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New PCNSL guidelines emphasize importance of patient fitness

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Micrograph showing PCNSL

New guidelines on the diagnosis and management of patients with primary central nervous system lymphoma (PCNSL) emphasize prompt diagnosis, aggressive treatment whenever possible, and multidisciplinary team support.

A unique aspect for hematologic cancers, the guidelines note, is that appropriate treatment for PCNSL requires input from neurology specialists.

And the guidelines recommend methotrexate-based treatment only be administered at centers experienced in delivering intensive chemotherapy.

Christopher P. Fox, MD, of the Nottingham University Hospitals NHS Trust in Nottingham, U.K., and his colleagues on behalf of the British Society for Haematology published the guidelines in BJH.

The authors incorporated findings from studies published since the society’s last comprehensive PCNSL guidelines were issued more than a decade ago.

The new guidelines provide recommendations for diagnosis and imaging, primary treatment of PCNSL, consolidation chemotherapy, follow-up, management of relapsed/refractory disease, and neuropsychological assessments.

Highlights include:

  • People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists
  • Histological diagnoses in addition to imaging findings should be performed
  • Corticosteroids should be avoided or discontinued before biopsy, as even a short course of steroids can impede diagnosis
  • Aggressive induction treatment should be chosen based on the patient’s fitness
  • Patients should be offered entry into clinical trials whenever possible
  • Universal screening for eye involvement should be conducted.

Primary treatment

Dr. Fox and his colleagues say definitive treatment for PCNSL—induction of remission followed by consolidation—should start within 2 weeks of diagnosis, and a treatment regimen should be chosen according to a patient’s physiological fitness, not age.

The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immuno-chemotherapy incorporating high-dose methotrexate (HD-MTX)—optimally, four cycles of HD-MTX, cytarabine, thiotepa, and rituximab.

Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab, and procarbazine, the guidelines say.

If patients cannot tolerate HD-MTX, oral chemotherapy, whole-brain radiotherapy (WBRT), or corticosteroids may be used.

The authors do not recommend intrathecal chemotherapy alongside systemic CNS-directed therapy.

Response should be assessed with contrast-enhanced magnetic resonance imaging (MRI) routinely after every two cycles of HD-MTX-based therapy and at the end of remission induction.

Consolidation chemotherapy

Consolidation therapy should be initiated after induction for all patients with non-progressive disease. High-dose thiotepa-based chemotherapy with autologous stem cell transplant (ASCT) is the recommended first-line option for consolidation.

Patients ineligible for high-dose therapy followed by ASCT who have residual disease after induction therapy should be considered for WBRT. This is also the case for patients with residual disease after thiotepa-based ASCT.

However, Dr. Fox and his colleagues say WBRT consolidation is “contentious” for patients in complete response after HD-MTX regimens but ineligible for ASCT. The authors suggest carefully balancing potential improvement in progression-free survival against risks of neurocognitive toxicity.

Response to consolidation, again measured with contrast-enhanced MRI, should be carried out between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.

Patients with relapsed or refractory disease should be approached with maximum urgency—the guidelines offer an algorithm for retreatment options—and offered clinical trial entry wherever possible.

Some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne and/or F. Hoffman-La Roche. 

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Image by Michael Bonert
Micrograph showing PCNSL

New guidelines on the diagnosis and management of patients with primary central nervous system lymphoma (PCNSL) emphasize prompt diagnosis, aggressive treatment whenever possible, and multidisciplinary team support.

A unique aspect for hematologic cancers, the guidelines note, is that appropriate treatment for PCNSL requires input from neurology specialists.

And the guidelines recommend methotrexate-based treatment only be administered at centers experienced in delivering intensive chemotherapy.

Christopher P. Fox, MD, of the Nottingham University Hospitals NHS Trust in Nottingham, U.K., and his colleagues on behalf of the British Society for Haematology published the guidelines in BJH.

The authors incorporated findings from studies published since the society’s last comprehensive PCNSL guidelines were issued more than a decade ago.

The new guidelines provide recommendations for diagnosis and imaging, primary treatment of PCNSL, consolidation chemotherapy, follow-up, management of relapsed/refractory disease, and neuropsychological assessments.

Highlights include:

  • People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists
  • Histological diagnoses in addition to imaging findings should be performed
  • Corticosteroids should be avoided or discontinued before biopsy, as even a short course of steroids can impede diagnosis
  • Aggressive induction treatment should be chosen based on the patient’s fitness
  • Patients should be offered entry into clinical trials whenever possible
  • Universal screening for eye involvement should be conducted.

Primary treatment

Dr. Fox and his colleagues say definitive treatment for PCNSL—induction of remission followed by consolidation—should start within 2 weeks of diagnosis, and a treatment regimen should be chosen according to a patient’s physiological fitness, not age.

The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immuno-chemotherapy incorporating high-dose methotrexate (HD-MTX)—optimally, four cycles of HD-MTX, cytarabine, thiotepa, and rituximab.

Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab, and procarbazine, the guidelines say.

If patients cannot tolerate HD-MTX, oral chemotherapy, whole-brain radiotherapy (WBRT), or corticosteroids may be used.

The authors do not recommend intrathecal chemotherapy alongside systemic CNS-directed therapy.

Response should be assessed with contrast-enhanced magnetic resonance imaging (MRI) routinely after every two cycles of HD-MTX-based therapy and at the end of remission induction.

Consolidation chemotherapy

Consolidation therapy should be initiated after induction for all patients with non-progressive disease. High-dose thiotepa-based chemotherapy with autologous stem cell transplant (ASCT) is the recommended first-line option for consolidation.

Patients ineligible for high-dose therapy followed by ASCT who have residual disease after induction therapy should be considered for WBRT. This is also the case for patients with residual disease after thiotepa-based ASCT.

However, Dr. Fox and his colleagues say WBRT consolidation is “contentious” for patients in complete response after HD-MTX regimens but ineligible for ASCT. The authors suggest carefully balancing potential improvement in progression-free survival against risks of neurocognitive toxicity.

Response to consolidation, again measured with contrast-enhanced MRI, should be carried out between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.

Patients with relapsed or refractory disease should be approached with maximum urgency—the guidelines offer an algorithm for retreatment options—and offered clinical trial entry wherever possible.

Some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne and/or F. Hoffman-La Roche. 

Image by Michael Bonert
Micrograph showing PCNSL

New guidelines on the diagnosis and management of patients with primary central nervous system lymphoma (PCNSL) emphasize prompt diagnosis, aggressive treatment whenever possible, and multidisciplinary team support.

A unique aspect for hematologic cancers, the guidelines note, is that appropriate treatment for PCNSL requires input from neurology specialists.

And the guidelines recommend methotrexate-based treatment only be administered at centers experienced in delivering intensive chemotherapy.

Christopher P. Fox, MD, of the Nottingham University Hospitals NHS Trust in Nottingham, U.K., and his colleagues on behalf of the British Society for Haematology published the guidelines in BJH.

The authors incorporated findings from studies published since the society’s last comprehensive PCNSL guidelines were issued more than a decade ago.

The new guidelines provide recommendations for diagnosis and imaging, primary treatment of PCNSL, consolidation chemotherapy, follow-up, management of relapsed/refractory disease, and neuropsychological assessments.

Highlights include:

  • People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists
  • Histological diagnoses in addition to imaging findings should be performed
  • Corticosteroids should be avoided or discontinued before biopsy, as even a short course of steroids can impede diagnosis
  • Aggressive induction treatment should be chosen based on the patient’s fitness
  • Patients should be offered entry into clinical trials whenever possible
  • Universal screening for eye involvement should be conducted.

Primary treatment

Dr. Fox and his colleagues say definitive treatment for PCNSL—induction of remission followed by consolidation—should start within 2 weeks of diagnosis, and a treatment regimen should be chosen according to a patient’s physiological fitness, not age.

The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immuno-chemotherapy incorporating high-dose methotrexate (HD-MTX)—optimally, four cycles of HD-MTX, cytarabine, thiotepa, and rituximab.

Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab, and procarbazine, the guidelines say.

If patients cannot tolerate HD-MTX, oral chemotherapy, whole-brain radiotherapy (WBRT), or corticosteroids may be used.

The authors do not recommend intrathecal chemotherapy alongside systemic CNS-directed therapy.

Response should be assessed with contrast-enhanced magnetic resonance imaging (MRI) routinely after every two cycles of HD-MTX-based therapy and at the end of remission induction.

Consolidation chemotherapy

Consolidation therapy should be initiated after induction for all patients with non-progressive disease. High-dose thiotepa-based chemotherapy with autologous stem cell transplant (ASCT) is the recommended first-line option for consolidation.

Patients ineligible for high-dose therapy followed by ASCT who have residual disease after induction therapy should be considered for WBRT. This is also the case for patients with residual disease after thiotepa-based ASCT.

However, Dr. Fox and his colleagues say WBRT consolidation is “contentious” for patients in complete response after HD-MTX regimens but ineligible for ASCT. The authors suggest carefully balancing potential improvement in progression-free survival against risks of neurocognitive toxicity.

Response to consolidation, again measured with contrast-enhanced MRI, should be carried out between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.

Patients with relapsed or refractory disease should be approached with maximum urgency—the guidelines offer an algorithm for retreatment options—and offered clinical trial entry wherever possible.

Some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne and/or F. Hoffman-La Roche. 

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