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.

Impact of modern treatment strategies on second cancer incidence for patients with early stage seminoma: A population-based study in British Columbia.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 423-423
Author(s):  
Gaurav Bahl ◽  
Rima Sanjay Pathak ◽  
Jenny J. Ko ◽  
Michael Sia ◽  
Gale Bowering ◽  
...  
Keyword(s):  
British Columbia ◽  
Radiation Therapy ◽  
Active Surveillance ◽  
Cumulative Incidence ◽  
Early Stage ◽  
Incidence Rates ◽  
Stage I ◽  
Second Cancers ◽  
Significant Difference

423 Background: The purpose of this study is to examine the incidence of Second Cancers (SC) in patients with Stage I or II Seminoma treated in British Columbia (BC), and compare rates between patients managed with Radiation Therapy, Chemotherapy, or Active Surveillance. Methods: Consecutive patients with Stage I or II Seminoma (n = 1549, 21167 person years) diagnosed in British Columbia between 1984 and 2013 were identified from the BC Cancer Registry and included in this study. Patients were managed with Radiation Therapy (RT; n = 663), Chemotherapy (CT; n = 259) or Active Surveillance (AS; n = 624). Data was extracted from the registry and verified by individual patient chart review. Cumulative incidence rates were computed using competing risk analysis. Age and Sex Standardized Incidence Ratios (ASIR) were calculated (compared to the Canadian population). Results: After a median follow-up of 14 years (RT group: 21.5yrs, CT group: 10yrs, AS group: 8yrs), the 15 year Overall Survival was 91.4%. Only 15 patients died from progressive Seminoma, while 46 died from second cancers. A total of 115 patients developed SCs, and the cumulative incidence (CI) of SC, at 15 years, was: 5.9% for patients who received RT, 8.6% for those who had CT, and 4.9% for patients managed with AS. The higher CI for patients treated with CT, versus RT, was not statistically significant (p = 0.08). The ASIR for RT, CT and AS groups were 1.31 (95% Confidence Intervals: 0.92- 1.86), 2.57 (1.07- 6.15; p = 0.03), and 1.38 (0.75- 2.54), respectively. Patients who underwent treatment at ages 30-44yr and 45-59yr had a significantly higher ASIRs of 4.33 (2.1- 8.9; p < 0.001) and 1.8 (1.16- 2.8; p = 0.008). ASIR was not significantly different when stratified by radiation dose, field types, or year of diagnosis. Conclusions: We found no statistically significant difference in the Cumulative Incidence of Second Cancers for patients treated with Radiation Therapy versus Chemotherapy in our patient population. Longer follow-up for the CT group is required to confirm trends evident in our analysis.

scholarly journals Comparative Effectiveness of Proton Therapy versus Photon Radiotherapy in Adolescents and Young Adults for Classical Hodgkin Lymphoma

2021 ◽  
Author(s):  
James E. Bates ◽  
Stephanie Terezakis ◽  
Christopher G. Morris ◽  
Avani D. Rao ◽  
Shuchi Sehgal ◽  
...  
Keyword(s):  
Young Adults ◽  
Hodgkin Lymphoma ◽  
Proton Therapy ◽  
Early Stage ◽  
Significant Risk ◽  
Adolescents And Young Adults ◽  
Classical Hodgkin Lymphoma ◽  
Significant Difference ◽  
Radiotherapy Dose ◽  
Photon Radiotherapy

Abstract Purpose Early stage (stages I-II) classical Hodgkin lymphoma (cHL) is a highly curable disease typically diagnosed in adolescents and young adults (AYAs). Proton therapy can also reduce the late toxicity burden in this population, but data on its comparative efficacy with photon radiotherapy in this population are sparse. We assessed outcomes in AYAs with cHL in a multi-institution retrospective review. Materials and Methods We identified 94 patients aged 15 to 40 years with stages I and II cHL treated with radiotherapy as part of their initial treatment between 2008 and 2017. We used Kaplan-Meier analyses and log-rank testing to evaluate survival differences between groups of patients. Results A total of 91 patients were included in the analysis. The 2-year progression-free survival (PFS) rate was 89%. Of the 12 patients who experienced progression after radiotherapy, 4 occurred out-of-field, 2 occurred in-field, and 6 experienced both in- and out-of-field progression. There was no significant difference in 2-year PFS among AYA patients by radiotherapy dose received (≥ 30 Gy, 91%; &lt; 30 Gy, 86%; P = .82). Likewise, there was no difference in 2-year PFS among patients who received either proton or photon radiotherapy (proton, 94%; photon, 83%; P = .07). Conclusion Our cohort of AYA patients had comparable outcomes regardless of radiotherapy dose or modality used. For patients with significant risk of radiation-induced late effects, proton therapy is a reasonable treatment modality.

scholarly journals Cause-Specific Mortality Following Initial Chemotherapy in a Population-Based Cohort of Patients With Classical Hodgkin Lymphoma, 2000-2016

2020 ◽  
Vol 38 (35) ◽  
pp. 4149-4162
Author(s):  
Graça M. Dores ◽  
Rochelle E. Curtis ◽  
Nicole H. Dalal ◽  
Martha S. Linet ◽  
Lindsay M. Morton
Keyword(s):  
Heart Disease ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Cancer Registries ◽  
The United States ◽  
Population Based ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Standardized Mortality Ratios

PURPOSE Mortality for patients with classical Hodgkin lymphoma (cHL) treated during an era characterized in the United States by widespread use of doxorubicin, bleomycin, vinblastine, and dacarbazine and diminishing use of radiotherapy is not well understood. PATIENTS AND METHODS We identified 20,007 individuals diagnosed with stage I/II (early) or III/IV (advanced) cHL between age 20 and 74 years treated with initial chemotherapy in US population-based cancer registries during 2000-2015 (follow-up through 2016). We used standardized mortality ratios (SMRs) to compare cause-specific relative mortality risk following cHL to that expected in the general population and estimated excess absolute risks (EARs; per 10,000 patient-years) to quantify disease-specific death burden. RESULTS We identified 3,380 deaths in the cHL cohort, including 1,321 (39%) not attributed to lymphoma. Overall, noncancer SMRs were increased 2.4-fold (95% CI, 2.2 to 2.6; observed, 559; EAR, 61.6) and 1.6-fold (95% CI, 1.4 to 1.7; observed, 473; EAR, 18.2) for advanced- and early-stage cHL, respectively, compared with the general US population. SMRs and EARs differed substantially by cause of death and cHL stage. Among the highest EARs for noncancer causes of death were those for heart disease (EAR, 15.1; SMR, 2.1), infections (EAR, 10.6; SMR, 3.9), interstitial lung disease (ILD; EAR, 9.7; SMR, 22.1), and adverse events (AEs) related to medications/drugs (EAR, 7.4; SMR, 5.0) after advanced-stage cHL and heart disease (EAR, 6.6; SMR, 1.7), ILD (EAR, 3.7; SMR, 13.1), and infections (EAR, 3.1; SMR, 2.2) after early-stage cHL. Strikingly elevated SMRs for ILD, infections, and AEs were observed < 1 year after cHL. Individuals age 60-74 years with advanced-stage cHL experienced a disproportionate excess of deaths as a result of heart disease, ILD, infections, AEs, and solid tumors. CONCLUSION Despite evolving cHL treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and cHL treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.

Excess Mortality Among 10-Year Survivors of Classical Hodgkin Lymphoma in Adolescents and Young Adults

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 694-694
Author(s):  
Ana Xavier ◽  
Luciano J. Costa
Keyword(s):  
Cardiovascular Disease ◽  
Young Adults ◽  
Cardiovascular Diseases ◽  
Hodgkin Lymphoma ◽  
Causes Of Death ◽  
Excess Mortality ◽  
Mortality Rates ◽  
Classical Hodgkin Lymphoma

Background: Adolescents and young adults (AYA) surviving classical Hodgkin Lymphoma (cHL) commonly face significant treatment-related morbidity that can result in premature death. It is not known if changes in therapy in recent years have resulted in reduction of excess mortality among long-term survivors of AYA-cHL. Methods: We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-18) to determine the excess mortality rate (EMR) for 10-year survivors of cHL. We included patients age 15-39 years diagnosed with cHL as first malignant neoplasm from 1993 until 2003. Cases reported from death certificates or autopsy only were excluded. Follow up was updated at the end of 2013. EMR was calculated using the difference between the observed mortality in the cohort of interest and the adjusted expected mortality among age, gender and race-matched individuals in the general population. Results: A total of 6,480 cases of cHL were included in the analysis with median follow up of 42.5 months. Median age of patients was 27 years at the time of diagnosis, 3,172 (48.9%) were male, 4,405 (68%) had stage I or II, 1,750 (27%) had stage III or IV, and in 325 (5%) cases stage was not available. Most patients were non-Hispanic white (4,783, 73.8%), 761 (11.7%) Hispanic, 615 (9.5%) non-Hispanic black, 276 (4.3%) other ethnicity, and 45 (0.7%) unknown. Five thousand and sixty eight (78.2%) had nodular sclerosis cHL, 616 (9.5%) had mixed-cellularity cHL, 606 (9.4%) had cHL non-otherwise specified, 153 (2.4%) had lymphocyte-rich cHL, and 37 (0.57%) had lymphocyte depleted cHL. The 15-year, 18-year, and 20-year EMR for 10-year survivors was 2.19% (95% C.I, 1.69%-2.86%), 3.48% (95% C.I. 2.57%-4.64%) and 4.07% (95% C.I. 2.53%-6.52%), respectively. EMR among 10 year AYA cHL survivors with diagnosis between 1993 and 2003 was substantially improved when compared to a similar cohort of 5,870 survivors with diagnosis between 1973 and 1992 (Figure 1). EMR at 15 and 18 years of diagnosis was higher among survivors of stage III-IV cHL than among survivors of stages I-II (Figure 2a), and higher at 15 years among males than female survivors (Figure 2b). Use of radiation therapy for early stage disease did not seem to affect the risk of excess mortality among 10-year survivors (Table). Causes of death were similar for stages I-II vs. stages III-IV. Most common causes of death were second malignancy (27.2%), cardiovascular disease (19%), and Hodgkin lymphoma (18.5%). Among male survivors there was a higher proportion of deaths due to cardiovascular disease (23.7% vs. 11.5%, p <0.038). Conclusion: Excess mortality rates for 10-year survivors of AYA-cHL has decreased with adoption of less toxic therapies. However, mortality rates continue high for several years for long term AYA HL survivors, mainly due to second malignancies and cardiovascular diseases. Less toxic therapies, control of cardiovascular diseases and implementation of cancer prevention programs for survivors of AYA-cHL are needed. Table. Table. Disclosures Costa: Sanofi: Honoraria, Research Funding.

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Sapna Pradyuman Patel ◽  
Hussein Abdul-Hassan Tawbi ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Tumor Location ◽  
Initial Diagnosis ◽  
Stage I ◽  
Acral Lentiginous Melanoma ◽  
Primary Tumor Location ◽  
Cns Metastasis ◽  
Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

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