Nodular lymphocyte-predominant and classical Hodgkin lymphoma subtypes: Differences in biology, survival, and impact of radiotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8550-8550
Author(s):  
Shihab Ali ◽  
Adam J. Olszewski
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Treatment Strategies ◽  
Relative Survival ◽  
Parametric Models ◽  
Steady Increase ◽  
Secondary Malignancies ◽  
Early Stage Disease ◽  
Immortal Time Bias ◽  
The Impact

8550 Background: Hodgkin lymphoma (HL) is a heterogeneous disease, but differences between nodular lymphocyte predominant (NLPHL) and classical (CHL) subtypes were previously studied in small cohorts preventing adjustment for confounders. We studied those differences based on the Surveillance, Epidemiology and End Results (SEER) program data. Methods: We analyzed SEER HL cases aged 16 years and over, diagnosed between 1995 and 2009. We studied the following endpoints: crude probability of HL-related death (HLRD), relative survival (using individual data in multivariate flexible parametric models) and risk of secondary malignancies (using competing risk regression). We studied the impact of radiotherapy (RT) in early-stage disease using a propensity score, adjusting for treatment selection and immortal time bias. Results: We identified 25,903 patients, with disparate age, race and stage distributions between subtypes. In a multivariate model, NLPHL demonstrated significantly better crude and net survival outcomes (Table), but in contrast to all CHL subtypes, it showed a steady increase in mortality rate after 2 years. The risk of secondary non-Hodgkin lymphoma was significantly higher in both NLPHL (hazard ratio, HR, 2.28, P=0.002) and lymphocyte-rich (LR) CHL (HR 2.08, P=0.01) than in nodular sclerosis (NS). The risk of other secondary malignancies did not differ between subtypes. After balancing confounding factors in treatment arms, RT in stage I/II was associated with improved survival in NS (HR, 0.78, P=0.001) and LR-CHL (HR 0.36, P<0.001), but not in NLPHL (HR 0.98, P=0.94) or in the remaining CHL subtypes. Conclusions: Studies of NLPHL and CHL subtypes should account for their disparate biology and clinical course. Prospective evaluation of NLPHL treatment strategies without RT is justified. [Table: see text]

Favorable Early-Stage Hodgkin Lymphoma

2006 ◽  
Vol 4 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Joachim Yahalom
Keyword(s):  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Combined Modality Therapy ◽  
Treatment Strategies ◽  
Cooperative Groups ◽  
Early Stage Disease ◽  
Bulky Disease ◽  
Combined Modality ◽  
Radiotherapy Alone

The category of favorable early-stage Hodgkin lymphoma (HL) includes patients with Ann Arbor stages I or II disease with no bulky disease or B symptoms. The precise definition of favorable versus unfavorable early-stage disease may vary among American and European cooperative groups. The overall 10-year survival rate of patients with favorable early-stage HL exceeds 90%. Indeed, effective treatments for this group of patients have been available for more than 4 decades. However, treatment strategies have radically changed over the past 15 years and focus now on maintaining the high cure rate while reducing the risk of treatment-related long-term morbidity. The optimal treatment is still evolving, and more recently, reduction in the total amount of chemotherapy and in radiation field and dose has shown excellent results. Combined modality therapy is the preferred treatment for patients with classical favorable early-stage HL (nodular sclerosis or mixed cellularity histology). Patients with early-stage lymphocyte predominance HL are highly curable using involved-field radiation therapy (IFRT) alone and do not require chemotherapy. Classical favorable HL is also curable with radiotherapy alone or with chemotherapy alone, but larger fields and higher-dose radiation or longer chemotherapy is required compared with combined modality. The freedom from treatment failure rate is significantly better with a combination of short chemotherapy and IFRT than with either chemotherapy or radiotherapy alone. Although combined modality is the standard preferred treatment for favorable disease, radiation therapy alone or chemotherapy alone could be considered under special circumstances or as part of an investigational protocol.

How I treat nodular lymphocyte-predominant Hodgkin lymphoma

Blood ◽  
2020 ◽  
Vol 136 (26) ◽  
pp. 2987-2993
Author(s):  
Dennis A. Eichenauer ◽  
Andreas Engert
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Treatment Options ◽  
Relative Survival ◽  
Treatment Modalities ◽  
High Dose ◽  
Combined Modality Treatment ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Stage Ia

Abstract Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with distinct pathologic and clinical characteristics. Unlike the malignant cells in classical Hodgkin lymphoma, the disease-defining lymphocyte-predominant cells in NLPHL are consistently positive for CD20, but do not express CD30. The clinical course of NLPHL is indolent in the majority of cases. Most patients present with early-stage disease at the initial diagnosis. First-line treatment of stage IA NLPHL usually consists of limited-field radiotherapy alone. Patients with early-stage NLPHL other than stage IA and intermediate-stage disease mostly receive combined-modality treatment, whereas individuals with advanced NLPHL are treated with chemotherapy alone. In relapsed NLPHL, conventional chemotherapy, anti-CD20 antibodies, and radiotherapy represent active treatment modalities. Only patients with poor-risk characteristics such as early disease recurrence are candidates for aggressive salvage treatment with high-dose chemotherapy and autologous stem cell transplantation. The overall and relative survival of patients with NLPHL is excellent as indicated by a low excess mortality compared with the general population. This article discusses treatment options for patients with NLPHL and factors that influence the choice of therapy on the basis of the available data and 2 clinical cases.

Results of the 2nd Planned Interim Analysis of the RAPID Trial (involved field radiotherapy versus no further treatment) in Patients with Clinical Stages 1A and 2A Hodgkin Lymphoma and a ‘negative’ FDG-PET Scan after 3 Cycles ABVD

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 369-369 ◽  
Author(s):  
John Radford ◽  
Michael O’Doherty ◽  
Sally Barrington ◽  
Wendi Qian ◽  
Philippa Patrick ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Interim Analysis ◽  
Early Stage ◽  
Randomised Trial ◽  
Pet Scan ◽  
Imaging Data ◽  
Early Stage Disease ◽  
Involved Field ◽  
The Impact ◽  
Involved Field Radiotherapy

Abstract The goal of response adapted treatment in Hodgkin lymphoma (HL) is to maximise the number of cures whilst minimising the effects of late toxicity on the incidence of endocrine dysfunction, infertility, second cancers and cardiovascular disease. In early stage disease abbreviated chemotherapy (CT) followed by involved field radiotherapy (RT) is the current standard of care but some patients (pts) may be cured by CT alone. If it were possible to identify this population, RT and associated toxicity could then be avoided in a proportion of pts using a response adapted approach. 18FDG-positron emission tomography (PET) provides an opportunity to identify pts with an excellent prognosis after CT but the impact on disease control of de-escalating treatment (no consolidation RT) based on these imaging data requires careful evaluation. Here we present results of the 2nd planned interim analysis of an ongoing randomised trial (RAPID) comparing no further treatment with involved field RT following 3 cycles ABVD and a ‘negative’ (-ve) PET scan. Consenting pts with histologically proven, previously untreated HL, stages 1A and 2A above the diaphragm are eligible for trial entry. Following 3 cycles ABVD, responders have a PET scan performed at one of 13 UK imaging centres (all calibrated for quality control purposes by phantom imaging) and if this is reported -ve for HL (score 1 or 2 on a 5 point scale) following central review at the Core Lab in London, pts are randomised between involved field RT and no further treatment. Those with a PET scan ‘positive’ (+ve) for HL (score 3, 4 or 5) have a 4th cycle of ABVD and involved field RT. When 320 PET -ve pts have been randomised the trial is powered to exclude a 10% difference in PFS with 90% power. At the time of analysis in May 2008, 369 pts (190 male, 179 female; median age 34.5 yrs) had been registered since trial activation in October 2003. Following 3 cycles ABVD, 331 have had a PET scan which at central review has been allocated a score of 1 (n=203, 61%), 2 (n=58, 18%), 3 (n=35, 11%), 4 (n=20, 6%) or 5 (n=15, 4%) giving an overall PET -ve rate (score 1 or 2) of 79%. 255 PET -ve pts have been randomised to receive involved field RT (n=125, 49%) or no further treatment (n=130, 51%). 6 pts have not been randomised (pt choice, 2; randomization data entered after database frozen for analysis, 2; clinician choice, 1; error, 1). After a median of 13 months from randomisation, 245 of 255 (96%) pts are alive and progression free, 6 (2%) have progressed and 4 (1.5%) have died (HL, 1; treatment related, 1; other 2). In this the 2nd planned, interim analysis of RAPID, we have shown that designation of PET -ve/+ve status at Core Lab review is feasible and patients are willing to undergo randomisation to answer a de-escalation of therapy question. The PET +ve rate of 21% after 3 cycles ABVD is at the upper end of the expected range and the event rate after short follow-up is very low. Accrual continues with an extended recruitment target of 535 to facilitate exclusion of a 7% difference between the randomised arms. This is based on views obtained from a survey undertaken at the 7th International Symposium on Hodgkin lymphoma (Cologne, Germany, 2007)1 1 Capturing expert opinion at an international meeting (IM) to understand what constitutes a practice changing result in an NCRN clinical trial featuring de-escalation of treatment in Hodgkin lymphoma (HL). Radford J et al, NCRI conference, Birmingham UK, October 2008

Aggressive Salivary Malignancies at Early Stage: Outcomes and Implications for Treatment

2017 ◽  
Vol 126 (7) ◽  
pp. 525-529 ◽  
Author(s):  
Robert W. Eppsteiner ◽  
Jonathan W. Fowlkes ◽  
Carryn M. Anderson ◽  
Robert A. Robinson ◽  
Nitin A. Pagedar
Keyword(s):  
Radiation Therapy ◽  
Early Stage ◽  
Relative Survival ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Adjuvant Radiation ◽  
Major Salivary Gland ◽  
High Grade ◽  
Duct Carcinoma ◽  
The Impact ◽  
Case Basis

Background: Few studies have examined whether the use of adjuvant treatment impacts survival for early stage high-grade salivary tumors. Methods: A retrospective review of the SEER database between 1973 and 2012 was performed. Patients with high-grade major salivary gland tumors including salivary duct carcinoma, carcinoma ex-pleomorphic adenoma, high-grade mucoepidermoid carcinoma, or adenocarcinoma, NOS were identified. Only stage I-II tumors were included. The impact of radiation status on observed and relative survival was examined. Results: Five hundred seventy-four patients with high-grade, early stage salivary tumors met inclusion criteria. Sixty-seven percent of patients received radiation therapy. There was no difference in observed or relative survival based on having received radiation. Conclusions: Adjuvant radiation is indicated for advanced stage tumors or early stage tumors with adverse features. For early stage tumors without adverse features, there was no survival benefit from radiation therapy. Adjuvant radiation should be decided on a case-by-case basis for these patients.

Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 406-413 ◽  
Author(s):  
Michelle Fanale
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Radiation Treatment ◽  
Early Stage ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Relapsed Disease

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic entity, with only ∼ 500 new cases in the United States per year with a similar infrequent incidence worldwide. NLPHL also has distinctive pathobiology and clinical characteristics compared with the more common classical Hodgkin lymphoma (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic cells and an overall more indolent course with a higher likelihood of delayed relapses. Given the limited numbers of prospective NLPHL-focused trials, management algorithms historically have typically been centered on retrospective data with guidelines often adopted from cHL and indolent B-cell lymphoma treatment approaches. Key recent publications have delineated that NLPHL has a higher level of pathological overlap with cHL and the aggressive B-cell lymphomas than with indolent B-cell lymphomas. Over the past decade, there has been a series of NLPHL publications that evaluated the role of rituximab in the frontline and relapsed setting, described the relative incidence of transformation to aggressive B-cell lymphomas, weighed the benefit of addition of chemotherapy to radiation treatment for patients with early-stage disease, considered what should be the preferred chemotherapy regimen for advanced-stage disease, and even assessed the potential role of autologous stem cell transplantation for the management of relapsed disease. General themes within the consensus guidelines include the role for radiation treatment as a monotherapy for early-stage disease, the value of large B-cell lymphoma–directed regimens for transformed disease, the utility of rituximab for treatment of relapsed disease, and, in the pediatric setting, the role of surgical management alone for patients with early-stage disease.

Treatment of Lung Cancer in Medically Compromised Patients

2016 ◽  
pp. e484-e491
Author(s):  
Jeffrey Crawford ◽  
Paul Wheatley-Price ◽  
Josephine Louella Feliciano
Keyword(s):  
Lung Cancer ◽  
Socioeconomic Status ◽  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Care Delivery ◽  
Advanced Lung Cancer ◽  
Early Stage Disease ◽  
Major Barrier ◽  
The Impact

Outcomes for patients with lung cancer have been improved substantially through the integration of surgery, radiation, and systemic therapy for patients with early-stage disease. Meanwhile, advances in our understanding of molecular mechanisms have substantially advanced our treatment of patients with advanced lung cancer through the introduction of targeted therapies, immune approaches, improvements in chemotherapy, and better supportive care. However, the majority of these advances have occurred among patients with good functional status, normal organ function, and with the social and economic support systems to be able to benefit most from these treatments. The aim of this article is to bring greater attention to management of lung cancer in patients who are medically compromised, which remains a major barrier to care delivery. Impaired performance status is associated with poor outcomes and correlates with the high prevalence of cachexia among patients with advanced lung cancer. CT imaging is emerging as a research tool to quantify muscle loss in patients with cancer, and new therapeutics are on the horizon that may provide important adjunctive therapy in the future. The benefits of cancer therapy for patients with organ failure are poorly understood because of their exclusion from clinical trials. The availability of targeted therapy and immunotherapy may provide alternatives that may be easier to deliver in this population, but clinical trials of these new agents in this population are vital. Patients with lower socioeconomic status are disproportionately affected by lung cancer because of higher rates of tobacco addiction and the impact of socioeconomic status on delay in diagnosis, treatment, and outcomes. For all patients who are medically compromised with lung cancer, multidisciplinary approaches are particularly needed to evaluate these patients and to incorporate rapidly changing therapeutics to improve outcomes.

scholarly journals Effect of Radiotherapy in Addition to Surgery in Early Stage Endometrial Cancer: A Population-Based Study

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3814
Author(s):  
Daniel Medenwald ◽  
Susan Langer ◽  
Cornelia Gottschick ◽  
Dirk Vordermark
Keyword(s):  
Endometrial Cancer ◽  
General Population ◽  
Early Stage ◽  
Relative Survival ◽  
Cancer Registries ◽  
Additional Treatment ◽  
Survival Models ◽  
Robert Koch Institute ◽  
Lower Survival Rate ◽  
The Impact

Background: The role of radiotherapy in the management of early (FIGO I) endometrial cancer is controversial with limited availability of prospective data from randomized trials. Methods: German Epidemiologic Cancer Registries provided by the Robert Koch Institute. We considered FIGO I cases with recorded operative treatment (n = 12,718, 2000–2017). We computed hazard ratios (HR) from relative survival models in relation to the mortality of the general population with 95% confidence intervals (CI). Multivariate models were adjusted for age, stage (IA vs. IB), grading, and chemotherapy. Radiotherapy included external radiotherapy and brachytherapy. Results: Cases with a favorable risk profile (FIGO IA, G1/G2) had a slightly lower survival rate, relative to the general population (FIGO IA: 0.9, G1: 0.91). The proportion of FIGO IA cases was lower in the radiotherapy group (52.6%) vs. cases without radiotherapy (78.6%). Additional treatment with radiotherapy was beneficial in FIGO IB (HR = 0.74) and all histopathological grades, but not FIGO IA cases (HR = 0.93) cases. Compared to IA tumors, IB cases had a HR of 1.51 (95% CI: 1.34–1.7). Conclusions: Radiotherapy in addition to surgery is beneficial for patients in a FIGO IB stage. Further studies need to address the impact of new techniques and risk assessment.

EARLY Interim FDG-PET Scan in Localised Hodgkin Lymphoma: Evaluation of Practice in 5 French Centers

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4935-4935
Author(s):  
Olivier Fitoussi ◽  
Pauline Brice ◽  
Sandrine Hirt ◽  
Philippe Solal-Celigny ◽  
Marie-Sarah Dilhuydy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Early Stage ◽  
Dose Intensity ◽  
Pet Scan ◽  
Treatment Intensification ◽  
Term Survival ◽  
Early Stage Disease ◽  
Fdg Pet Scan ◽  
Pre Treatment

Abstract Background: Long-term survival from Hodgkin lymphoma (HL) in early-stage (I–II) patients is more than 85%. However, certain patients have a primary refractory disease with a worse evolution. Early interim FDG-PET scan performed after 2 courses of chemotherapy (PET-2) provides an early and accurate assessment of response and a correlation has been demonstrated between normalization of PET-2 and patient outcome. Aim: To evaluate the percentage of negative PET-2 in early-stage patients, and to seek clinical or biological factors predictive of positive PET-2. Methods: Sixty-five patients from five French centers with early-stage Hodgkin lymphoma received ABVD as firstline chemotherapy. PET-2 was performed 3 weeks after the second course of ABVD. Radiotherapy and changes in management according to FDG-PET scan result could be decided by the clinician. Evaluation was retrospective. Results: The median age was 36 years (range17–77). Thirty-nine patients were male. Seventy-three percent of patients were in unfavorable group according to EORTC criteria (one or more of the following criteria: age &gt; 50, systemic symptoms, elevated ESR &gt;50 mm, bulk disease and more than three lymph node areas involved). Fifty-seven patients had a pre-treatment FDGPET scan with a modification of staging in 6 cases. Initial staging according to CT scan or FDG-PET scan was as follows: IA: 5 patients, IB: no patient, IIA: 35 patients and IIB: 25 patients. Fifty-three patients (82%) had a negative PET-2 whereas 12 patients (18%) had a clearly positive PET-2. Among the 53 patients with negative PET-2, 47 patients underwent radiation therapy after completion of four courses of ABVD. Among the 12 patients with positive PET-2, treatment intensification (BEACOPP) occurred for 7 patients with a negative FDG-PET scan for 6 of them after two courses. For the 5 PET+ patients pursuing with ABVD: three had a negative FDG-PET scan and two had a positive FDGPET scan after four cycles of ABVD. At a median follow-up of 30 months, 6 patients relapsed early after the end of the treatment (2 in the negative PET-2 group and 4 in the positive PET-2 group). Out of the 7 patients of the positive PET-2 group receiving an increase dose intensity of chemotherapy (BEACOPP), 3 of them relapsed. The 59 other patients did not presented any failure or relapse at the present time. Conclusion: We showed in this series that negative PET-2 is obtained in 82% of patients with early stage disease. These results are similar to those expected in the EORTC H10 trial which evaluates PET-2 guided treatment adaptation and expect about 85–90% of negative PET-2. This retrospective study augurs that positive TEP2 is a pejorative prognostic factor and the utilisation of the BEACOPP treatment in these population remains to define. Prospective studies, like H10 EORTC trial are warranted to confirm these results and find predictive factors for a positive PET-2.

Changes In The Use Of Radiation Therapy Among Adolescents and Young Adults With Early Stage Classical Hodgkin Lymphoma: Implications For Survival and Risk Of Secondary Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 722-722
Author(s):  
Ana Xavier ◽  
Luciano J Costa
Keyword(s):  
Young Adults ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Early Stage ◽  
Stage I ◽  
Secondary Malignancies ◽  
Classical Hodgkin Lymphoma

Abstract Background Early stage classical Hodgkin lymphoma (HL) is a highly curable disease with the combined use of chemotherapy and radiation therapy (RT). There has been a recent trend to abandon RT, driven mostly by concerns of development of secondary malignancies (SMN). However, it is unknown whether the omission of RT in adolescents and young adults (AYA) with early stage HL affects survival and the risk of developing SMN. Methods We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-13) to determine the overall survival (OS) and the risk of SMN among AYA with early stage HL treated or not with radiation therapy. Inclusion criterion was the diagnosis of stage I or II HL in the period of 1995-2010 as first malignant neoplasm among patients age 13 to 40 years. Patients with less than 6 months of follow up and patients with unknown use of RT were excluded. Follow up was updated to the end of 2012 (November 2012 submission). Cases were divided in two “eras”, 1995-2002 and 2003-2010, with the latter being expected to reflect changes in the use of RT. The impact of the era, RT, age, race, gender, and stage on survival were accessed utilizing multivariate analysis. Cumulative incidence of SMN among early stage HL survivors was calculated using a competing risk model, treating death from any cause in absence of SMN as the competing risk. Results A total of 5,336 early stage HL cases were included in the analysis with median follow up of 89 months (range 7-191). Median age of patients was 27 years, 2,459 (46%) were male, 1,327 (24.8%) had stage I, 512 (9.7%) had classical HL non otherwise specified, 4,231 (79.2%) had nodular sclerosing HL, 442 (8.3%), had mixed-cellularity HL, 130 (2.4%) had lymphocyte-rich HL, and 21 (0.4%) had lymphocyte depleted HL. Most patients were white (4,438; 83.2%), 513 (9.6%) black, 337 (6.4%) other ethnicity, and 44 (0.8%) unknown. There where 2,793 patients in the 1995-2002 era and 2,542 patients in the 2003-2010 era. Radiation was included in the initial treatment of 1,659 (59.4%) patients in the former and 1,351 (53%) patients in the latter era (P<0.001). Factors associated with use of RT were earlier era, white race and stage II HL. Within the 1995-2002 era, there was a trend towards better survival among patients treated with RT (5-year survival 95.0% vs. 93.6%, P=0.058). In the 2003-2010 cohort survival was superior among patients treated with RT (5-year survival 97.3% vs. 95.9%, P=0.008). In multivariate analysis, diagnosis of HL in the 1995-2002 era (HR=1.73, 95% C.I. 1.31-2.28, P < 0.001), black race (HR= 2.18, 95% C.I. 1.63-2.91, P <0.001), male sex (HR=1.55, 97% C.I. 1.24-1.93, P < 0.001), and omission of RT (HR=1.31, 95% C.I. 1.05-1.64, P=0.017) were associated with higher mortality. The cumulative incidence of SMN was not significantly different between patients treated or not with radiation, while the risk of death was higher among patients not treated with RT (Figure). Conclusion There has been a reduction in utilization of RT among AYA with early stage HL in the US. Omission of RT was associated with increased overall mortality but no reduction in incidence of SMN and should not be adopted outside clinical trials. Disclosures: No relevant conflicts of interest to declare.

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