NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023.

Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021.

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody-drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1-mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

Risk and subtypes of secondary primary malignancies in diffuse large B-cell lymphoma survivors change over time based on stage at diagnosis.

BACKGROUND: Previous studies have shown an increased risk of secondary primary malignancies (SPMs) after diffuse large B-cell lymphoma (DLBCL) treatment. Whether stage of DLBCL at diagnosis affects the subtypes of SPMs that occur has not been previously described. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients aged >18 years diagnosed with primary DLBCL from 1973 to 2010 and categorized by early stage (ES) (stage I-II) or advanced stage (AS) (stage III-IV) disease. Differences in overall and location-specific SPM incidence by stage and time since diagnosis were assessed in 5-year intervals using a Fine-Gray hazards model. Overall survival was compared using the log-rank test. A Cox proportional hazards model was used to assess differences in survival. RESULTS: In total, 26,038 patients with DLBCL were identified, including 14,724 with ES and 11,314 with AS disease. The median follow-up was 13.3 years. Overall, 13.0% of patients developed SPM, with a higher but nonsignificantly increased risk of SPM development in those who had ES disease compared with those who had AS disease (14% vs 11.6%; P = .14). During the first 5 years after diagnosis, patients who had ES disease had a higher risk of SPM than those who had AS disease, specifically colorectal, pancreas, breast, and prostate SPMs. During the period from 10 to 15 years after diagnosis, patients who had AS disease had a higher risk of SPM than those who had ES disease, specifically hematologic SPMs. Development of SPM was found to significantly increase the risk of death regardless of stage at diagnosis. CONCLUSIONS: In this large, population-based study, distinctly different subtypes and temporal patterns of SPM development were identified based on stage of DLBCL at diagnosis. The current study merits consideration of tailored site-specific and time-specific surveillance for patients with DLBCL according to stage and time interval since diagnosis.

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.

BACKGROUND: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. METHODS: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. FINDINGS: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. INTERPRETATION: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. FUNDING: National Cancer Institute, US Department of Health and Human Services.

Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

Integration of automation into an existing clinical workflow to improve efficiency and reduce errors in the manual treatment planning process for total body irradiation (TBI).

PURPOSE: To identify causes of error, and present the concept of an automated technique that improves efficiency and helps to reduce transcription and manual data entry errors in the treatment planning of total body irradiation (TBI). METHODS: Analysis of incidents submitted to incident learning system (ILS) was performed to identify potential avenues for improvement by implementation of automation of the manual treatment planning process for total body irradiation (TBI). Following this analysis, it became obvious that while the individual components of the TBI treatment planning process were well implemented, the manual 'bridging' of the components (transcribing data, manual data entry etc.) were leading to high potential for error. A C#-based plug-in treatment planning script was developed to remove the manual parts of the treatment planning workflow that were contributing to increased risk. RESULTS: Here we present an example of the implementation of "Glue" programming, combining treatment planning C# scripts with existing spreadsheet calculation worksheets. Prior to the implementation of automation, 35 incident reports related to the TBI treatment process were submitted to the ILS over a 6-year period, with an average of 1.4 ± 1.7 reports submitted per quarter. While no incidents reached patients, reports ranged from minor documentation issues to potential for mistreatment if not caught before delivery. Since the implementation of automated treatment planning and documentation, treatment planning time per patient, including documentation, has been reduced; from an average of 45 min pre-automation to <20 min post-automation. CONCLUSIONS: Manual treatment planning techniques may be well validated, but they are time-intensive and have potential for error. Often the barrier to automating these techniques becomes the time required to "re-code" existing solutions in unfamiliar computer languages. We present the workflow here as a proof of concept that automation may help to improve clinical efficiency and safety for special procedures.

NCCN Guidelines Insights: B-Cell Lymphomas, Version 3.2019.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin's lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial.

BACKGROUND: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. METHODS: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial. FINDINGS: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group. INTERPRETATION: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT. FUNDING: National Cancer Institute.

Thiotepa-Based Intensified Reduced-Intensity Conditioning Adult Double-Unit Cord Blood Hematopoietic Stem Cell Transplantation Results in Decreased Relapse Rate and Improved Survival Compared with Transplantation Following Standard Reduced-Intensity Conditioning: A Retrospective Cohort Comparison.

The "Minnesota" reduced-intensity conditioning (RIC) cord blood transplantation (CBT) regimen (standard RIC) of fludarabine (Flu) (200 mg/m2), cyclophosphamide (Cy) (50 mg/kg), and 200- or 300-cGy total body irradiation (TBI) is the most published RIC CBT regimen. Though well tolerated, high relapse rates remain a concern with this regimen. Intensification of conditioning may reduce relapse without increasing transplant-related mortality (TRM). We performed a retrospective cohort comparison of outcomes in adult patients who underwent first double-unit CBT with standard RIC as compared with the intensified regimen of Flu 150 mg/m2, Cy 50 mg/kg, thiotepa 10 mg/kg, and 400-cGy TBI (intensified RIC). Of the 99 patients studied, 47 received intensified RIC. Acute myelogenous leukemia was the major indication for transplant. The median age at transplant was 67 years (range, 24 to 74 years) and 54 years (range, 25 to 67 years) in standard RIC and intensified RIC, respectively. Median hematopoietic stem cell transplantation comorbidity index was 3 (range, 0 to 5) and 1 (range, 0 to 6) in the standard RIC and intensified RIC groups, respectively. Median follow-up among survivors was 22 months (range, 3.7 to 79 months) following standard RIC and 15 months (range, 2.8 to 36 months) following intensified RIC. The cumulative incidence (CI) of relapse was significantly lower following intensified RIC compared with standard RIC (P = .0013); this finding maintained significance in multivariate analysis (P = .045). TRM was comparable between the 2 groups (P = .99). Overall survival (OS) was significantly improved following intensified RIC as compared with standard RIC (P = .03). Median OS was 17 months following standard RIC versus not reached followed intensified RIC. The CI of grade II to IV acute graft-versus-host disease (GVHD) was significantly higher in the intensified RIC cohort than the standard RIC-cohort (P = .007), while CI of grade III to IV acute GVHD, any chronic GVHD, and moderate-to-severe chronic GVHD was comparable in each cohort (P = .20, P = .21, and P = .61, respectively). This retrospective analysis shows an improvement in OS and decreased relapse without increase in TRM in patients receiving intensified RIC as compared with standard RIC. Our data suggest that consideration of thiotepa-based intensified RIC may improve outcomes in fit, older patients undergoing double-unit CBT.

NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor-positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20-0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26-0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25-1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017.

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL.

Hodgkin Lymphoma Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

Diffuse Large B-Cell Lymphoma Version 1.2016.

Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes.

NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016.

Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.

Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared.

Breast Cancer Following Radiation for Hodgkin Lymphoma: Clinical Scenarios and Risk-Reducing Strategies.

Since most patients with Hodgkin lymphoma survive their disease, long-term issues such as development of second primary malignancies arise, especially in patients treated with multimodal therapy including radiation therapy plus chemotherapy. The risk of breast cancer is significantly elevated in women exposed to high-dose ionizing radiation to the chest before age 40. The case of a 48-year-old patient with a lump in her right breast is presented as a clinical scenario in this article. We review available strategies for screening and risk reduction through chemoprevention or risk-reducing surgery, as well as challenges for management of breast cancer in patients with prior exposure to radiation for Hodgkin lymphoma. The Children's Oncology Group clinical practice guidelines for long-term follow-up care of pediatric cancer survivors provide recommendations that have been endorsed by American and European oncologists.