Clinical Oncology: Case Reports

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Perspective, Clin Oncol Case Rep Vol: 5 Issue: 10

Therapy Development for Diffuse Large B-cell Lymphoma in its Limited Stage

Alan Walker*

Editorial Office, Clinical Oncology: Case Reports, United Kingdom

*Corresponding Author: Alan Walker
Editorial Office, Clinical Oncology: Case Reports, United Kingdom
E-mail: [email protected]

Received: October 04, 2022; Manuscript No: COCR-22-79483;
Editor Assigned: October 06, 2022; PreQC Id: COCR-22-79483 (PQ);
Reviewed: October 20, 2022; QC No: COCR-22-79483 (Q);
Revised: October 22, 2022; Manuscript No: COCR-22-79483 (R);
Published: October 29, 2022; DOI: 10.4172/cocr.5(10).257

Citation: Walker A (2022) Therapy Development for Diffuse Large B-cell Lymphoma in its Limited Stage. Clin Oncol Case Rep 5:10


The most prevalent Non-Hodgkin Lymphoma (NHL) is Diffuse Large B-Cell Lymphoma (DLBCL), with limited-stage DLBCL being classified as stage I or stage II illness. Advanced-stage DLBCL differs from early-stage DLBCL in risk classification, initial treatment options, and recurrence patterns, however there is little information on the influence of biologic characteristics on outcome. Patients achieve outstanding results, with a 2-year survival rate of almost 90%. Sequential prospective trials and sizable registry studies have assessed the ideal number of chemotherapy cycles and applied PET-adapted strategies to lessen the requirement for radiotherapy during the past few years. Bulky disease, extra nodal disease, totally resected situations, and unfavorable biologic characteristics including high-grade B-cell lymphoma with double/triple hit rearrangements still require special attention.

Keywords: Cancer immunotherapy; Radiotherapy; Non-Hodgkin Lymphoma; Lymphoma


The most prevalent Non-Hodgkin Lymphoma (NHL), Diffuse Large B-Cell Lymphoma (DLBCL), accounts for roughly one-fourth of all new NHL cases each year in the United States. It is physiologically diverse; formerly, limited-stage disease was described as a disease having sites that could be covered by a single radiation field and was Ann Arbor stage 1 or 2. According to the Lugano criteria, restricted or early-stage disease is currently classified as stage 1 or stage 2, and advanced stage disease as stage 3 or stage 4. Bulky illness, which has different definitions in the literature, is a crucial modification to traditional staging and is covered in more detail below. The majority of anatomic sites of disease are in the head and neck region, including Waldeyer's ring, and cervical lymph nodes, according to large descriptive studies. Patients with limited-stage disease are typically in their sixth decade of life, with a small male predominance. Whether the distinction between limited and advanced stage reflects earlier diagnosis of a disease or a biologically unique entity with various risks and outcomes aspects is still up for debate. SWOG 8736 has an impact on how limited-stage DLBCL is being treated. In the years between 1988 and 1995, during the pre-rituximab era, this phase 3 trial established mixed modality therapy as a standard of care. According to SWOG S8736, Radiation Therapy (RT) combined with three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was not inferior to eight rounds of CHOP alone. The cornerstone for subsequent limited-stage disease trials has remained to be this definition of new standard treatment duration and the inclusion of radiation for patients with limited-stage diseases.

Additionally, SWOG S8736 created a risk stratification score system for limited-stage DLBCL that is still useful today. By excluding extra nodal locations and categorizing stage as either 1 or 2, the International Prognostic Index (IPI) for DLBCL was modified to better stratify prognosis in limited-stage illness. Thus, the age > 60 years, stage 2 disease, raised serum Lactate Dehydrogenase (LDH) and performance status of two or above each receive one point in this stage-modified IPI (smIPI). In the pre-rituximab era, stage I illness patients without risk factors had the greatest outcomes, with a 5-year Overall Survival (OS) rate of 95%; stage 1 patients with one to two risk factors had a 5-year OS rate of 77%; and patients with three or more risk factors had a 5-year OS rate of 50%. Compared to simple age-adjusted risk stratification, this smIPI model proved more effective. Results in each IPI risk group have improved in the rituximab era across both limited and advanced illness groups, and smIPI is still useful.

Similar to how it works for advanced-stage DLBCL, the anti-CD20 monoclonal antibody rituximab increases survival in limited-stage disease. According to the MabThera International Trial (MInT) research, R-CHOP treatment improved 6-year Event-Free Survival (EFS) to 84.3% and 6-year Overall Survival (OS) to 94.9% compared to CHOP alone in non-bulky, limited-stage illness. It's noteworthy that these survival advantages happened in long-term follow-up without a discernible rise in toxicity or incidence of subsequent hematologic malignancy. The superiority of chemo immunotherapy in younger patients with limited-stage DLBCL and a fair prognosis was established by this study. In the current period, the management of patients with limited-stage DLBCL has progressed, reevaluating the function of Radiotherapy (RT), the ideal duration of systemic therapy, and the developing use of metabolic imaging by Positron Emission Tomography (PET) in response-adapted management. As diagnostics and therapeutics continue to advance in the contemporary day, this review will concentrate on medicines and research concentrating on limited-stage DLBCL, the inherent difficulties and potential future considerations for this condition, and our suggested strategy to these individuals.

The necessity to take into account specific populations that may require modified treatment approaches persists as modern treatment approaches to limited-stage DLBCL have evolved to shorter periods of chemo-immunotherapy and maybe omit RT when combining PET-based response assessments. There is no information directing treatment in the very elderly, so our strategy is to choose R-CHOP, R-mini-CHOP, or R-CEOP, which are similar to techniques in advanced-stage disease, but restrict the number of cycles for younger individuals, which is similar to ways in limited-stage disease. The following section discusses the cases of bulky disease, DHL and DEL, extra nodal involvement, CNS prophylaxis, and totally resected illness. Among limited-stage DLBCL, bulky disease is variously defined; the majority of limited-stage studies do not include stage 2 bulky disease, and bulky stage 1 illness is a rather uncommon condition. Although definitions of bulk vary, several studies compare bulky stage 2 illness to advanced stage DLBCL. Since patients with bulky diseases were not included in studies like FLYER, LYSA/GOELAMS 02-03, SWOG 0014, and S1001-all of which were described above-many of their conclusions must be used with caution in the case of patients with bulky diseases. In the UNFOLDER trial, extranodal disease was included, and patients with bulky disease were randomized to receive chemo immunotherapy with or without RT. Because there were too many patients with bulky diseases in the non-RT arm who failed to meet the predetermined criteria, the research was prematurely ended. However, there was no difference in PFS or OS (3-year PFS of 89% vs. 81%; 3-year OS of 93% each) between groups getting RT or not. These events were attributed to partial responses needing localized RT. 190 patients with limited stage cancer were included in a different analysis from MD Anderson, however it was retrospective; 54% of them had radiation therapy, and 48% of them had bulky disease (defined as having a diameter of at least 5 cm).

The majority of these studies have had difficulty conclusively addressing the issue of bulky limited-stage illness, in part due to the small sample size of this subpopulation. This unanswered topic was the focus of a recent retrospective research in Finland that also used iPET. A total of 123 patients with all-stage DLBCL and bulky disease got RT at a rate of 44%. The existence of a bulky tumor was linked to a worse prognosis in patients with limited-stage disease, with a 2-year PFS of 53% as opposed to 90% for those with non-bulky disease; however, the effect of RT in postponing time to progression vanished after eliminating primary refractory cases. Additionally, they pointed out that in cases with bulky disease, a negative iPET maintained its prognostic advantage, with a 2-year PFS of 87% for patients with a negative iPET and bulky disease compared to 57% for patients with a positive iPET. This study, which is retrospective in nature, suggests that RT offers an additional benefit in cases of bulky limited-stage disease, such as primary refractory disease, but it also emphasizes that a negative iPET retains its prognostic power even in the presence of other risk factors, suggesting that RT may not always be necessary.


DHL and DEL's prognostic value in limited-stage illness is not fully understood. An earlier retrospective analysis of DHL patients made the suggestion that RT might help low-risk DHL patients by lengthening the period until relapse. A recent retrospective analysis, concentrating on limited-stage MYC-rearranged cases, revealed that the overall response rate to chemo immunotherapy was 91% among 104 patients. The CR rate for rearrangements involving DHL was 75% as opposed to 98% for those using MYC alone. The 2-year PFS and OS for the overall sample were 78% and 86%, respectively, and there was no difference between DHL patients or those receiving RT. Additionally, there was no evidence to support the use of aggressive chemo immunotherapy over R-CHOP for either DHL or MYC-only rearranged instances in limited-stage patients. Although the number of cases is very small, these findings collectively imply that DHL or DEL instances of limited-stage disease may have a different outcome than what is anticipated in advanced-stage disease. There isn't now a clear role for increased treatment for these populations; we need further research to characterize these distinctions.

The entire tumor may be removed during the diagnostic biopsy in some cases with limited-stage illness or in other rare circumstances, such as blockage from intestine extra nodal involvement. These individuals often received the same amount of therapy for the same amount of time as other patients with limited-stage diseases. Although this varies depending on the initial site of the cancer and other factors, subgroup analyses of previous studies have sought to better address the question of whether totally resected disease allows for shorter therapy. The goal of CISL 12-09, a phase 2 study by the Consortium for Improving Survival of Lymphoma (CISL), was to assess the efficacy and safety of a shortened three-cycle R-CHOP regimen following total resection of limited stage illness. Only one patient out of 22 had advanced at the median follow-up time of 39.5 months, and the predicted 2-year OS was 95%. Five years of extended follow-up revealed no new instances of illness progression or fatalities. This supports a restricted systemic therapy course for individuals with totally resected limited stage DLBCL, despite the study's size limitations. 52 patients had entirely resected stage I disease by baseline PET, according to an analysis of patients who were participated in the Positron Emission Tomography-guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) experiment. The majority of these patients had 6 cycles of R-CHOP. Under 60-year-old patients who had their disease surgically removed had an improved 2-year PFS and OS of 100% compared to 92% and 95%, respectively, for patients who had their disease incompletely removed. For patients over 60-years-old, there were no statistically significant differences between groups. Furthermore, it is fair to predict that four cycles of chemo immunotherapy would be sufficient based on the findings of the FLYER trial mentioned above.

A retrospective study of 250 patients with mostly intestinal, limited-stage cancer who received six cycles of CHOP or R-CHOP revealed that the combined surgery and chemotherapy group had a significantly higher CR rate of 85% compared to the chemotherapy alone group, which also experienced more local relapses. Surgery was performed on 60% of patients for bulk excision and 31% for blockage. In contrast to 52 and 62% for chemotherapy alone, surgically resected patients had a 3-year PFS and 3-year OS of 82% and 91%, respectively. However, surgical excision of intestinal illness cases in advanced stages did not improve survival. Importantly, this study indicates that whereas surgical resection may not improve survival in limited-stage cancer due to anatomical reasons, it may do so in advanced-stage disease


Patients with DLBCL at the restricted stage currently have excellent results, and the research has advanced to reduce both short- and long-term toxicity without sacrificing efficacy. Patients who have had their illness completely removed may be treated with a maximum of four cycles of R-CHOP without consolidative radiotherapy if they have a low smIPI or negative iPET. Additional radiation and/or chemo immunotherapy may have a survival benefit for people who have a positive iPET. In addition, people with bulky (>7.5 cm) or extra nodal disease should try RT, with specific recommendations for each situation as previously mentioned. Such a strategy reduces the negative effects of therapy without compromising the positive results. There are still other considerations that must be taken into account, such as Central Nervous System (CNS) prophylaxis for high-risk disease sites like testicular, breast, and nasopharyngeal involvement, and constrained treatment regimens for those who have fully resected illness at staging. The significance of early iPET in lowering the requirement for additional therapy will be better clarified in upcoming research in restricted stage DLBCL. Further research into the restricted DLBCL disease biology is also necessary to improve our comprehension of a potential new categorization for DLBCL that may not be only based on stage. This may alter the diagnosis and treatment of limited-stage DLBCL and has the potential to further enhance results and toxicity in a condition that has advanced significantly in the period of contemporary medicine.

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