Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.

Management and Outcomes of Patients with Refractory Solitary Plasmacytoma after Treatment with Definitive Radiation Therapy.

PURPOSE: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes. METHODS AND MATERIALS: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes. RESULTS: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT dose was 45 Gy, and median follow-up was 71 months from end of RT. Fifteen patients had additional treatment for refractory disease at a median time of 9.5 months after RT, with the following subsequent interventions: surgical resection (n = 4), additional RT (n = 2), systemic therapy without evidence of multiple myeloma (MM; n = 4), systemic therapy for progression to MM (n = 5), and observation (n = 2). Of 4 patients treated with surgical resection, 3 progressed to MM 22 to 43 months after diagnosis. Of 2 patients treated with additional RT, neither responded, and both had pathologic confirmation of residual disease after the second course. Four patients treated with systemic therapy without MM all had complete responses on positron emission tomography and no subsequent MM progression. Eight patients were initially observed after RT for ≥12 months (n = 8) or ≥24 months (n = 6). Of the 2 patients in continued observation, both had stable/unchanged avidity after radiation treatment for 12 and 22 months and ultimately had a slow decrease of disease avidity over multiple years. CONCLUSIONS: Patients with RT-refractory SPs can achieve good local control with alternative therapies, such as surgery or systemic therapy, if needed. Additional RT does not seem to be effective. Given the known high rates of progression from SP to MM, close observation of asymptomatic persistent disease until disease progression is likely sufficient in most cases.

Radiation Therapy Can Be Safely Incorporated into Pretransplantation Treatment Regimens for Patients with Multiple Myeloma.

Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 106 CD34+/kg PBPCs (range, .5 to 54.8× 106 CD34+/kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 106 CD34+/kg PBPCs, and 166 (83%) collected >5.0 × 106 CD34+/kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma.

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma.

Purpose: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). Methods and Materials: We performed a single institutional retrospective review of 44 patients who received BVRT. Results: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P = .047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease. Conclusions: Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control.

Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation: A Phase 2 Trial of Daily Partial Breast Irradiation.

PURPOSE: Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled. METHODS AND MATERIALS: We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost. RESULTS: All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P = .004), breast pain (P = .004), and physician-reported cosmesis (P < .001). CONCLUSIONS: Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

Central Nervous System Prophylaxis and Treatment in Acute Leukemias.

OPINION STATEMENT: Improvements in systemic therapy in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have improved patient outcomes and reduced the incidence of CNS relapse. However, management of patients with CNS disease remains challenging, and relapses in the CNS can be difficult to salvage. In addition to treatment with CNS-penetrant systemic therapy (high-dose methotrexate and cytarabine), intrathecal prophylaxis is indicated in all patients with ALL, however is not uniformly administered in patients with AML without high-risk features. There is a limited role for radiation treatment in CNS prophylaxis; however, radiation should be considered for consolidative treatment in patients with CNS disease, or as an option for palliation of symptoms. Re-examining the role of established treatment paradigms and investigating the role of radiation as bridging therapy in the era of cellular therapy, particularly in chemotherapy refractory patients, is warranted.

Second malignancies in patients with Hodgkin's Lymphoma: Half a century of experience.

Purpose: Therapeutic improvements for Hodgkin's Lymphoma (HL) has resulted in excellent survival outcomes. Thus, patients are increasing susceptible to developing secondary malignancy (SM) a feared iatrogenic complication. Materials & Methods: We evaluated the SM risk in a cohort of patients with HL treated over a 50-year period. In total, 1653 patients were treated for HL from 1956 to 2009 at a tertiary-cancer-center. A cumulative incidence function was used to quantify SM risk and the Fine and Gray competing risk model was used to identify disease and treatment related correlates. Results: Two-hundred-ninety patients (19%) developed SMs. Paradoxically, SM risk was higher in the modern era with 20-year cumulative incidence rates of 11.1%, 11.9%, 17% and 21.8%, for patients treated <1970, 1971-1986, 1986-1995 and 1996-2009, respectively. We hypothesized that the disproportionately high rate of early deaths in the early era may skew the assessment of SM risks, a much-delayed event. When the analysis was restricted to patients with early-stage favorable HL treated >1980, we found a reversal of the trend, especially on the risk of solid tumor, with a hazard ratio of 0.57 (p = 0.0651) in patients treated after 1996. Conclusion: Our findings highlight the limitations of comparing the risk of a late event between groups with disparate rates of early deaths, despite the use of a competing risk model. When partially corrected for, patients treated in the more recent time period experienced a lower solid tumor risk.

Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy.

Purpose: Long-term data regarding the disease control outcomes of proton beam therapy (PBT) for patients with favorable risk intact prostate cancer (PC) are limited. Herein, we report our institution's long-term disease control outcomes in PC patients with clinically localized disease who received PBT as primary treatment. Methods: One hundred sixty-six favorable risk PC patients who received definitive PBT to the prostate gland at our institution from 2010 to 2012 were retrospectively assessed. The outcomes studied were biochemical failure-free survival (BFFS), biochemical failure, local failure, regional failure, distant failure, PC-specific survival, and overall survival. Patterns of failure were also analyzed. Multivariate Cox proportional hazards modeling was used to estimate independent predictors of BFFS. Results: The median length of follow-up was 8.3 years (range, 1.2-10.5 years). The majority of patients had low-risk disease (58%, n = 96), with a median age of 64 years at the onset of treatment. Of 166 treated men, 13 (7.8%), 8 (4.8%), 2 (1.2%) patient(s) experienced biochemical failure, local failure, regional failure, respectively. Regional failure was seen in an obturator lymph node in 1 patient and the external iliac lymph nodes in the other. None of the patients experienced distant failure. There were 5 (3.0%) deaths, none of which were due to PC. The 5- and 8-year BFFS rate were 97% and 92%, respectively. None of the clinical disease characteristics or treatment-related factors assessed were associated with BFFS on multivariate Cox proportional hazards modeling (all P > .05). Conclusion: Disease control rates reported in our assessment of PBT were similar to those reported in previous clinically localized intact PC analyses, which used intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, or radical prostatectomy as definitive therapy. In addition, BFFS rates were similar, if not improved, to previous PBT studies.

Contemporary use and outcomes of radiation and chemotherapy for unresectable pancreatic cancer.

Background: We assessed radiation treatment (RT) use and complications for unresectable pancreatic cancer in the US, comparing conventionally fractionated (CFRT) and stereotactic body radiation treatment (SBRT) to inform real-world expected outcomes and practice. Material and Methods: We analyzed 5,624 patients with non-metastatic, unresectable pancreatic cancer (2,522 older patients age > 65, diagnosed 2006-2013 in Medicare linked data; and 3,102 younger patients age < 65, diagnosed 2006-2016 in MarketScan data), comparing CFRT vs. SBRT vs. chemotherapy alone. Cochran-Armitage tested temporal trends. Fisher's Exact Test and proportional hazards models compared gastrointestinal (GI) complications. Healthcare payments (Consumer Price Index adjusted to 2015) through 12 months were compared using generalized linear regression models with log link and gamma distribution. Results: RT use declined from 55% to 45% of older patients (2006-2013) and 52% to 47% of younger patients (2006-2016) (Ptrend < 0.001 both). Among RT patients, SBRT use increased to 10% of older patients and 12% of younger patients in the most recent years (Ptrend = 0.04 and < 0.001 respectively). Addition of RT was associated with more frequent GI bleeds, strictures, and fistulas (Δ= +3% to 9% excess events, all P ≤ 0.05). Temporal patterns suggested decreasing complications over time (Ptrend = 0.05 and 0.05 for older and younger patients). Among younger patients, there was no difference in GI complications for SBRT vs. CFRT (P > 0.05, all comparisons). Among older patients, increased complications were seen for SBRT in 1-4 fractions vs. CFRT (P < 0.05), but not SBRT in 5 fractions (P = 0.72). Healthcare payments were greatest for SBRT when compared with CFRT or chemotherapy under US Medicare (P < 0.001) and employer-based insurance (P < 0.001). Conclusion: Real-world treatment has shifted toward more selectivity for RT in unresectable pancreatic cancer. However, SBRT uptake and improving trends in complications profiles represent opportunities to optimize current use and benefit. Findings are applicable to inform future comparative and cost effectiveness models of RT for this disease.

Salvage radiotherapy for primary refractory and relapsed diffuse large B-Cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, accounting for 30-40% of all non-Hodgkin lymphoma cases and presenting later in life, most often in the sixth decade. Although DLBCL is curable, long-term remission rates are only 60-80%. The most recent major advance in upfront therapy for DLBCL was the monoclonal anti-CD20 antibody rituximab, which was approved in the late 1990s; now, 25 years later, up to 40% of patients will experience primary refractory or relapsed disease, thereby underscoring the importance of salvage therapy. Radiation therapy can be highly effective in DLBCL, both initially as consolidation therapy and later as salvage therapy and is currently being explored in the context of immune and cellular therapies. The aim of this review is to examine the therapeutic approaches for relapsed or refractory DLBCL, with a focus on whether using radiation therapy as salvage therapy can improve the likelihood of cure.

Prognostic value of disease distribution in secondary central nervous system diffuse large B cell lymphoma treated with radiation therapy.

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (p = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.

Radiation and CAR T-cell Therapy in Lymphoma: Future Frontiers and Potential Opportunities for Synergy.

CAR T-cell therapy has revolutionized the treatment approach to patients with relapsed/refractory hematologic malignancies; however, there continues to be opportunity for improvement in treatment toxicity as well as response durability. Radiation therapy can play an important role in combined modality treatments for some patients undergoing CAR T-cell therapy in various clinical settings. In this review, we discuss the current evidence for RT in the setting of CAR T-cell therapy for patients with hematologic malignancies and propose potential opportunities for future investigation of RT and CAR T-cell treatment synergy. Future research frontiers include investigation of hypotheses including radiation priming of CAR T-cell mediated death, pre-CAR T-cell tumor debulking with radiation therapy, and selection of high risk patients for early radiation salvage after CAR T cell therapy.

The impact of cell-of-origin, MYC/Bcl-2 dual expression and MYC rearrangement on disease relapse among early stage diffuse large B-cell lymphoma patients treated with combined modality therapy.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 - 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.

A Prospective Trial of Radiation Therapy Efficacy and Toxicity for Localized Mucosa-associated Lymphoid Tissue (MALT) Lymphoma.

PURPOSE: We report the long-term results of a prospective trial conducted to determine the efficacy and safety of radiation therapy (RT) alone in treating localized mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS AND MATERIALS: Patients with localized MALT lymphoma were eligible and treated with involved field RT to doses of 24 to 39.6 Gy. Relapse-free survival (RFS) was the primary endpoint. Kaplan-Meier analysis was used to estimate RFS, progression-free survival (PFS), and overall survival (OS) defined from time of study entry. Preplanned subgroup analyses were performed based on site of involvement. RESULTS: From 2000 to 2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years. Thirty-four patients had gastric MALT, 17 orbital, 13 head and neck nonorbit, 4 skin, and 5 disease of other sites. Thirteen of 34 patients with gastric MALT were Helicobacter pylori positive at the time of initial diagnosis and underwent 1 to 3 courses of triple antibiotic therapy. All gastric MALT patients had documented persistent MALT without H. pylori on endoscopy before enrollment in the study. All patients achieved a complete response with a median time of 3 months. Eleven patients (15%) had disease relapse, 9 of which were at sites outside the RT field with median time to progression of 38.3 months. Median PFS was 17.5 years, and median RFS and OS were not reached. The 10-year relapse-free rate was 83% (95% confidence interval [CI], 74%-93%). The 10-year PFS rate was 71% (95% CI, 60%-84%). The 10-year OS rate was 86% (95% CI, 77%-96%). RFS, PFS, and OS did not differ by disease site (P = .17, .43, and .50, respectively). All relapses were successfully salvaged. One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow-up, and no patient died of MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2, with only 1 grade 3 toxicity. Twenty-two patients (30%) experienced late toxicity, with only 1 grade 3 toxicity. CONCLUSIONS: This prospective study confirms that RT for MALT lymphoma provides excellent long-term RFS with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further avoid treatment-related morbidity. CLINICALTRIALS.GOV: NCT04465162.

Partial omission of bleomycin for early-stage Hodgkin lymphoma patients treated with combined modality therapy: Does incomplete ABVD lead to inferior outcomes?

Classical Hodgkin lymphoma (HL) patients achieve excellent outcomes; therefore, treatment de-escalation strategies to spare toxicity have been prioritized. In a large randomized trial of early stage HL patients, omission of chemotherapeutic agents including bleomycin from the standard ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen was not found to be non-inferior; however the effect of partial omission is unknown. We investigated the effect of bleomycin omission on outcome for 150 early stage HL patients. At eight years, freedom from relapse was 99% for both patients who received complete or incomplete bleomycin, which is reassuring for patients requiring bleomycin omission due to toxicity.

Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy.

Importance: Response-adapted randomized trials have used positron emission tomography-computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective: To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants: This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography-computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures: 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures: The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results: The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance: In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

Decreased heart dose with deep inspiration breath hold for the treatment of gastric lymphoma with IMRT.

We hypothesized that deep inspiration breath-hold (DIBH) and computed-tomography image-guided radiotherapy (CT-IGRT) may be beneficial to decrease dose to organs at risk (OARs), when treating the stomach with radiotherapy for lymphoma. We compared dosimetric parameters of OARs from plans generated using free-breathing (FB) versus DIBH for 10 patients with non-Hodgkin lymphoma involving the stomach treated with involved site radiotherapy. All patients had 4DCT and DIBH scans. Planning was performed with intensity modulated radiotherapy (IMRT) to 30.6 Gy in 17 fractions. Differences in target volume and dosimetric parameters were assessed using a paired two-sided t-test. All heart and left ventricle parameters including mean dose, V30, V20, V10, and V5 were statistically significantly lower with DIBH. For IMRT-FB plans the average mean heart dose was 4.9 Gy compared to 2.6 Gy for the IMRT-DIBH group (p < 0.001). There was a statistically significant decrease in right kidney dose with DIBH. For lymphoma patients treated to the stomach with IMRT, DIBH provides superior OAR sparing compared to FB-based planning, most notably reducing dose to the heart and left ventricle. This strategy could be considered when treating other gastric malignancies.

Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma.

The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.