Role of Chemotherapy in Laryngeal Lymphoma
Systemic chemotherapy with rituximab plus anthracycline-based regimens (R-CHOP or modified R-CHOP) is the primary treatment for laryngeal diffuse large B-cell lymphoma, with radiotherapy reserved as consolidation in select cases.
Primary Treatment Approach
Chemotherapy forms the cornerstone of treatment for laryngeal DLBCL, following the same principles as nodal DLBCL. The larynx represents an extranodal site accounting for less than 1% of all primary laryngeal neoplasms, but the treatment paradigm mirrors systemic DLBCL management 1, 2.
Standard Chemotherapy Regimen
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is the established standard of care for DLBCL, including laryngeal presentations 3, 4.
The GELA trial demonstrated that R-CHOP in patients aged 60-80 years achieved complete response rates of 76% versus 63% with CHOP alone (P = 0.005), with 10-year progression-free survival of 36.5% versus 20% 3.
For localized disease (Stage I-II), treatment options include:
For advanced disease, 6-8 cycles of R-CHOP represent the standard approach 3, 4, 5.
Age and Comorbidity Modifications
Elderly patients or those with cardiac dysfunction may require dose-reduced regimens, such as R-COP (omitting doxorubicin) 1.
The feasibility of delivering full-dose CHOP therapy to elderly patients with myeloid growth factor support has been demonstrated, though toxicities and death rates from intercurrent illnesses are higher 3.
Complete response rates in patients aged 65-75 years are approximately 50%, but only 40% in those >75 years with standard CHOP 3.
Role of Radiotherapy
Radiotherapy serves as consolidation rather than primary treatment in laryngeal DLBCL.
For localized disease, chemoradiotherapy (3 cycles R-CHOP plus radiotherapy) demonstrated superior 5-year progression-free survival (77%) and overall survival (82%) compared to chemotherapy alone (64% and 72%, respectively) in the SWOG study 3.
However, more recent GELA trials in elderly patients with localized good-prognosis disease (IPI 0) showed that 4 cycles of CHOP alone were as effective as CHOP plus involved-field radiotherapy, with 5-year overall survival of 76% versus 67% 3.
The decision to add radiotherapy should be based on:
- Stage (I-II versus advanced)
- IPI score (low-risk may not require radiotherapy)
- Age and fitness (elderly patients may not benefit from added radiotherapy)
- Response to chemotherapy (PET-negative after chemotherapy may not require radiotherapy) 3
Treatment Algorithm by Clinical Scenario
Fit Patients with Localized Disease (Stage I-II, Low IPI)
- Administer 3-4 cycles of R-CHOP followed by involved-field radiotherapy (30-40 Gy) 3, 1
- Alternative: 6 cycles of R-CHOP alone if patient achieves complete metabolic response on interim PET 3
Fit Patients with Advanced Disease or High IPI
- Deliver 6-8 cycles of R-CHOP every 21 days 3, 4, 5
- Consider CNS prophylaxis for patients with high-intermediate or high IPI, especially with >1 extranodal site or elevated LDH 6
Elderly or Unfit Patients
- For patients aged >80 years or with significant cardiac dysfunction, use dose-reduced R-COP (omitting doxorubicin) for 6-8 cycles 1
- Consider 4 cycles of reduced-dose R-CHOP if localized disease with low IPI 3
- Growth factor support should be utilized to maintain dose intensity when possible 3
Critical Diagnostic Considerations
Laryngeal DLBCL diagnosis can be challenging and may require multiple biopsies.
- Repeated biopsies from the laryngeal lesion may be necessary when initial samples are insufficient 1, 2
- Consider biopsy of regional lymph nodes if they develop, as these may provide diagnostic tissue when laryngeal biopsies are non-diagnostic 1
- Flow cytometry should confirm CD20-positive B-cell population 4
Common Pitfalls to Avoid
Do not treat laryngeal DLBCL with radiotherapy alone—this is inadequate for systemic disease control and leads to high relapse rates 3
Do not omit rituximab from the treatment regimen—the addition of rituximab to CHOP significantly improves complete response rates, progression-free survival, and overall survival 3, 4
Do not automatically add radiotherapy to all elderly patients with localized disease—those >69 years with low-risk disease may have worse overall survival with added radiotherapy due to treatment-related toxicity 3
Do not delay treatment for extensive staging—laryngeal DLBCL should be treated promptly once diagnosis is confirmed, following standard DLBCL staging and risk stratification 1, 2