In the Journals

Chemoradiotherapy improves OS in unresected glioblastoma multiforme

Combined chemotherapy and radiation significantly improved OS over radiation alone in patients with glioblastoma multiforme who underwent biopsy alone, according to study results published in Cancer.

Concurrent chemoradiotherapy and adjuvant chemotherapy serves as the standard of care for patients with glioblastoma multiforme who undergo surgical resection. The efficacy of this therapeutic approach remained unclear in patients who only undergo a diagnostic biopsy.

James Yu

James B. Yu

“There are different reasons why a patient might not have surgery,” James B. Yu, MD, MHS, associate professor of therapeutic radiology and director of the prostate and genitourinary cancer program at Yale School of Medicine, told HemOnc Today. “Usually they have tumor that is theoretically unresectable or located in an area the surgeon cannot reach, or the patient is so ill that the surgeon doesn’t think he or she will survive the surgery. With those patients who are doing so poorly, the question oftentimes is whether it’s worthwhile to give radiation and chemotherapy, or to proceed toward palliative care.”

Although the trial that established chemoradiotherapy with temozolomide as the standard of care for patients with glioblastoma multiforme (Stupp R, et al. N Engl J Med. 20015;doi:10.1056/NEJMoa043330) included patients who underwent biopsy only, this cohort was too small to definitively identify a benefit, according to Yu.

Yu and colleagues used the National Cancer Data Base to identify 1,479 patients (median age at diagnosis, 61 years; 58.3% men) who underwent biopsy alone. Patients then received treatment with radiation alone (n = 154) or concurrent chemoradiotherapy with temozolomide (n = 1,325).

Three-quarters of the cohort (76%) had no significant comorbidities. The median time to radiation initiation after diagnosis was 24 days.

Patients who underwent chemoradiotherapy achieved a median OS of 9.2 months, compared with 5.6 months for those who underwent radiation alone (HR = 0.64; 95% CI, 0.54-0.76).

The survival benefit remained significant after the researchers adjusted for potential confounding factors, including age, sex, race, diagnosis year, comorbidity status and time to radiation receipt (adjusted HR = 0.71; 95% CI, 0.6-0.85).

The researchers observed an association between improved OS and patient age younger than 70 years (adjusted HR = 0.58; 95% CI, 0.51-0.65). However, initiation of radiation more than 30 days after diagnosis increased risk for mortality (adjusted HR = 1.16; 95% CI, 1.03-1.29).

Chemoradiotherapy remained significantly associated with better OS in a subgroup analysis of patients aged older than 70 years (HR = 0.68; 95% CI, 0.53-0.89).

A propensity score–matched analysis conducted to balance treatment groups for age, race, Charlson-Deyo score, and time for diagnosis to start of radiation continued to favor chemoradiotherapy (median, 8.4 months vs. 5.7 months; HR = 0.72; 95% CI, 0.56-0.93).

Study limitations included a lack of data on salvage therapies in the National Cancer Data Base, as well as the potential for selection bias, as older patients are more likely to receive radiation alone.

Further, the researchers excluded patients who did not complete a full course of conventionally fractionated radiation therapy, and thus patients included in the analysis who survived the duration of therapy may not represent of the overall patient population, which could contribute to shorter OS.

“This study highlights the fact that observational studies and clinical trials are complementary,” Yu said. “We took the finding from the clinical trial and validated it in a larger and more diverse cohort, leading to a confirmatory outcome. These data will encourage patients and providers to consider chemoradiotherapy as a more beneficial therapy in biopsy-only patients who can tolerate it. The field is moving that way already, but if there are doctors or treatment centers who are waiting for more evidence, this could serve to push them in that direction.” – by Cameron Kelsall

For more information:

James B. Yu, MD, MHS, can be reached at james.b.yu@yale.edu.

Disclosure: Yu reports institutional funding from 21st Century Oncology for research outside of the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Combined chemotherapy and radiation significantly improved OS over radiation alone in patients with glioblastoma multiforme who underwent biopsy alone, according to study results published in Cancer.

Concurrent chemoradiotherapy and adjuvant chemotherapy serves as the standard of care for patients with glioblastoma multiforme who undergo surgical resection. The efficacy of this therapeutic approach remained unclear in patients who only undergo a diagnostic biopsy.

James Yu

James B. Yu

“There are different reasons why a patient might not have surgery,” James B. Yu, MD, MHS, associate professor of therapeutic radiology and director of the prostate and genitourinary cancer program at Yale School of Medicine, told HemOnc Today. “Usually they have tumor that is theoretically unresectable or located in an area the surgeon cannot reach, or the patient is so ill that the surgeon doesn’t think he or she will survive the surgery. With those patients who are doing so poorly, the question oftentimes is whether it’s worthwhile to give radiation and chemotherapy, or to proceed toward palliative care.”

Although the trial that established chemoradiotherapy with temozolomide as the standard of care for patients with glioblastoma multiforme (Stupp R, et al. N Engl J Med. 20015;doi:10.1056/NEJMoa043330) included patients who underwent biopsy only, this cohort was too small to definitively identify a benefit, according to Yu.

Yu and colleagues used the National Cancer Data Base to identify 1,479 patients (median age at diagnosis, 61 years; 58.3% men) who underwent biopsy alone. Patients then received treatment with radiation alone (n = 154) or concurrent chemoradiotherapy with temozolomide (n = 1,325).

Three-quarters of the cohort (76%) had no significant comorbidities. The median time to radiation initiation after diagnosis was 24 days.

Patients who underwent chemoradiotherapy achieved a median OS of 9.2 months, compared with 5.6 months for those who underwent radiation alone (HR = 0.64; 95% CI, 0.54-0.76).

The survival benefit remained significant after the researchers adjusted for potential confounding factors, including age, sex, race, diagnosis year, comorbidity status and time to radiation receipt (adjusted HR = 0.71; 95% CI, 0.6-0.85).

The researchers observed an association between improved OS and patient age younger than 70 years (adjusted HR = 0.58; 95% CI, 0.51-0.65). However, initiation of radiation more than 30 days after diagnosis increased risk for mortality (adjusted HR = 1.16; 95% CI, 1.03-1.29).

Chemoradiotherapy remained significantly associated with better OS in a subgroup analysis of patients aged older than 70 years (HR = 0.68; 95% CI, 0.53-0.89).

A propensity score–matched analysis conducted to balance treatment groups for age, race, Charlson-Deyo score, and time for diagnosis to start of radiation continued to favor chemoradiotherapy (median, 8.4 months vs. 5.7 months; HR = 0.72; 95% CI, 0.56-0.93).

Study limitations included a lack of data on salvage therapies in the National Cancer Data Base, as well as the potential for selection bias, as older patients are more likely to receive radiation alone.

Further, the researchers excluded patients who did not complete a full course of conventionally fractionated radiation therapy, and thus patients included in the analysis who survived the duration of therapy may not represent of the overall patient population, which could contribute to shorter OS.

“This study highlights the fact that observational studies and clinical trials are complementary,” Yu said. “We took the finding from the clinical trial and validated it in a larger and more diverse cohort, leading to a confirmatory outcome. These data will encourage patients and providers to consider chemoradiotherapy as a more beneficial therapy in biopsy-only patients who can tolerate it. The field is moving that way already, but if there are doctors or treatment centers who are waiting for more evidence, this could serve to push them in that direction.” – by Cameron Kelsall

For more information:

James B. Yu, MD, MHS, can be reached at james.b.yu@yale.edu.

Disclosure: Yu reports institutional funding from 21st Century Oncology for research outside of the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures.