Modern Radiation for Hematologic Stem Cell Transplantation: Total Marrow and Lymphoid Irradiation or Intensity-Modulated Radiation Therapy Total Body Irradiation.

The development of large-field intensity-modulated radiation therapy (IMRT) has enabled the implementation of total marrow irradiation (TMI), total marrow and lymphoid irradiation (TMLI), and IMRT total body irradiation (TBI). IMRT TBI limits doses to organs at risk, primarily the lungs and in some cases the kidneys and lenses, which may mitigate complications. TMI/TMLI allows for dose escalation above TBI radiation therapy doses to malignant sites while still sparing organs at risk. Although still sparingly used, these techniques have established feasibility and demonstrated promise in reducing the adverse effects of TBI while maintaining and potentially improving survival outcomes.

Biology-Guided Radiation Therapy: An Evolving Treatment Paradigm.

Biology-guided radiation therapy is an emerging field whereby delivery of external beam radiotherapy incorporates biological/molecular imaging to inform radiation treatment. At present, there is evidence for the use of functional imaging such as PET to evaluate treatment response in patients both during and after radiation treatment as well as to provide a method of adapting or selecting patient-specific treatments. Examples in thoracic, gastrointestinal, and hematologic malignancies are provided. Improvements in PET metrics, thresholds, and novel radiotracers will further move this novel field forward.

ACR-ARS Practice Parameter for the Performance of Total Body Irradiation.

OBJECTIVES: This practice parameter was revised collaboratively by the American College of Radiology (ACR) and the American Radium Society (ARS). This practice parameter provides updated reference literature regarding both clinical-based conventional total body irradiation and evolving volumetric modulated total body irradiation. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. RESULTS: This practice parameter provides a comprehensive update to the reference literature regarding conventional total body irradiation and modulated total body irradiation. Dependence on dose rate remains an active area of ongoing investigation in both the conventional setting (where instantaneous dose rate can be varied) and in more modern rotational techniques, in which average dose rate is the relevant variable. The role of imaging during patient setup and the role of inhomogeneity corrections due to computer-based treatment planning systems are included as evolving areas of clinical interest notably surrounding the overall dose inhomogeneity. There is increasing emphasis on the importance of evaluating mean lung dose as it relates to toxicity during high-dose total body irradiation regimens. CONCLUSIONS: This practice parameter can be used as an effective tool in designing and evaluating a total body irradiation program that successfully incorporates the close interaction and coordination among the radiation oncologists, medical physicists, dosimetrists, nurses, and radiation therapists.

Difficulties in Defining Oligometastatic Prostate Cancer: Implications for Clinical Trial Accrual and Community Practice Adoption of Metastasis-Directed Therapy Approaches.

BACKGROUND: Metastasis-directed therapy is widely utilized for oligometastatic prostate cancer patients, but standard imaging does not always identify metastases definitively and, even with PSMA PET, there may be equivocal findings. Not all clinicians have access to detailed imaging review, particularly outside of academic cancer centers, and PET scan access is also limited. We sought to understand how imaging interpretation impacted recruitment to a clinical trial for oligometastatic prostate cancer. METHODS: IRB approval was obtained to review medical records from all patients screened for the institutional IRB-approved clinical trial for men with oligometastatic prostate cancer involving androgen deprivation plus stereotactic radiation to all metastatic sites, as well as radium223 (NCT03361735). Clinical trial inclusion required at least one bone metastatic lesion and no more than five total sites of metastasis, including soft tissue sites. Tumor board discussion records were reviewed, along with results from additional radiology studies ordered or confirmatory biopsies performed. Clinical characteristics such as PSA level and Gleason score were studied for association with likelihood of oligometastatic disease confirmation. RESULTS: At the time of data analysis, 18 subjects were deemed eligible and 20 were not eligible. The most common reasons for ineligibility were no confirmed bone metastasis in 16 patients (59%) and too many metastatic sites in 3 (11%). The median PSA of eligible subjects was 3.28 (range 0.4-45.5), whereas the median PSA of those found to be ineligible was 10.45 (range 3.7-26.3) when there were too many metastases identified, and 2.7 (range 0.2-34.5) when metastases were unconfirmed. PET imaging (PSMA or fluciclovine PET) increased the number of metastases, while MRI resulted in downstaging to non-metastatic disease. CONCLUSIONS: This research suggests that additional imaging (i.e., at least two independent imaging modalities of a possible metastatic lesion) or tumor board adjudication of imaging findings may be critical to correctly identify patients appropriate for enrollment in oligometastatic protocols. This should be considered as trials of metastasis-directed therapy for oligometastatic prostate cancer accrue and results are translated to broader oncology practice.

Long-Term Follow-Up of Bridging Therapies Prior to CAR T-Cell Therapy for Relapsed/Refractory Large B Cell Lymphoma.

BACKGROUND: Bridging therapy (BT) with systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). We report the long-term outcomes of the patients who received commercial CAR T-cell therapy with or without BT. METHODS: The patients with LBCL who underwent infusion of a commercial CD19 CAR T product were eligible. The radiation was stratified as comprehensive or focal. The efficacy outcomes and toxicity were analyzed. RESULTS: In total, 156 patients were included and, of them, 52.5% of the patients received BT. The median progression-free survival (PFS) was 0.65 years in the BT cohort compared to 1.45 years in the non-BT cohort. The median overall survival (OS) was 3.16 years in the BT cohort and was not reached in the non-BT cohort. The patients who received comprehensive radiation (versus focal) had significantly improved PFS and OS, achieving a 1-year PFS of 100% vs. 9.1% and 1-year OS of 100% vs. 45.5%. There was no difference in the severe toxicity between any of the nonbridging or BT cohorts. CONCLUSIONS: BT did not appear to compromise outcomes with respect to response rates, disease control, survival, and toxicity. The patients with limited disease treated with RT had favorable outcomes.

Stereotactic body radiation therapy to the kidney for metastatic renal cell carcinoma: A narrative review of an emerging concept.

This narrative review provides a historical overview of cytoreductive nephrectomy for metastatic renal cell carcinoma (mRCC) and examines the safety and therapeutic potential of cytoreductive stereotactic body radiation therapy (SBRT) for mRCC in the modern immunotherapy era. In the last five years, the introduction of immune checkpoint inhibitors for the treatment of mRCC has improved outcomes for patients. This has brought forth new exploration of the role of CN in combination with immunotherapy. Early retrospective evidence suggests that there may be a benefit of deferred CN after immunotherapy (IOT) for de novo mRCC patients. However, there has also been concern regarding the feasibility of surgery after IOT due to inflammation. SBRT may be an appropriate alternative in these circumstances. Since 1999, cytoreductive SBRT has been used for inoperable primary RCC. Several prospective and retrospective studies treating the kidney tumor for localized RCC have shown that this technique is safe and produces favorable and durable local control. SBRT has also exhibited similar effectiveness to CN, while providing additional benefits including noninvasiveness and the ability to treat tumors that can't be treated with nephrectomy or ablation due to size or location. Furthermore, SBRT confers immunostimulatory effects, which are hypothesized to work synergistically with immunotherapy. Clinicians should consider SBRT a safe and reliable alternative to CN for RCC patients. Ongoing studies are exploring the utility of SBRT for treatment of the primary tumor in mRCC patients receiving standard of care immunotherapy.

Genomic and Transcriptomic Predictors of Response from Stereotactic Body Radiation Therapy in Patients with Oligoprogressive Renal Cell Carcinoma.

Stereotactic body radiation therapy (SBRT) has been shown to be safe and effective for delaying systemic treatment change among patients with metastatic renal cell carcinoma (mRCC). In this study, we sought to assess the genomic signatures of patients with mRCC who underwent SBRT for oligoprogression. A total of 30 patients with oligoprogressive disease were identified, the majority of whom had clear cell renal cell carcinoma (83.3%) and were receiving first-line treatment (53.3%). Genomic and transcriptomic sequencing were available in 20 and 16 patients, respectively. Duration of systemic treatment (DOT) was categorized as that prior (DOT[P]) and subsequent (DOT[S]) to radiation treatment. The median DOT(P) and DOT(S) were 15.1 and 18.3 mo, respectively, with a median DOT(S)/DOT(P) ratio of 1.4. Patients who had a DOT(S)/DOT(P) ratio of ≥1 had increased expression in pathways related to cell proliferation and development. In contrast, among patients with a ratio of ≤1, the reactive oxygen species pathway was enriched. This study highlights the potential role of genomics and transcriptomics to refine radiation treatment selection in patients with mRCC. PATIENT SUMMARY: In this study, we looked at mutations and genomic expressions among kidney cancer patients who responded better to stereotactic body radiotherapy. We found that enriched expression of certain pathways might play a role in response to radiotherapy.

First-In-Human Pilot PET Immunoimaging Study of 64Cu-Anti-Carcinoembryonic Antigen Monoclonal Antibody (hT84.66-M5A) in Patients with Carcinoembryonic Antigen-Producing Cancers.

Background: PET imaging using radiolabeled immunoconstructs shows promise in cancer detection and in assessing tumor response to therapies. The authors report the first-in-human pilot study evaluating M5A, a humanized anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb), radiolabeled with 64Cu in patients with CEA-expressing malignancies. The purpose of this pilot study was to identify the preferred patient population for further evaluation of this agent in an expanded trial. Methods: Patients with CEA-expressing primary or metastatic cancer received 64Cu-DOTA-hT84.66-M5A with imaging performed at 1 and 2 days postinfusion. 64Cu-DOTA-hT84.66-M5A PET scan findings were correlated with CT, MRI, and/or FDG PET scans and with histopathologic findings from planned surgery or biopsy performed postscan. Results: Twenty patients received 64Cu-DOTA-hT84.66-M5A. Twelve patients demonstrated positive images, which were confirmed in 10 patients as tumor by standard-of-care (SOC) imaging, biopsy, or surgical findings. Four of the 8 patients with negative imaging were confirmed as true negative, with the remaining 4 patients having disease demonstrated by SOC imaging or surgery. All 5 patients with locally advanced rectal cancer underwent planned biopsy or surgery after 64Cu-DOTA-hT84.66-M5A imaging (4 patients imaged 6-8 weeks after completing neoadjuvant chemotherapy and radiation therapy) and demonstrated a high concordance between biopsy findings and 64Cu-DOTA-hT84.66-M5A PET scan results. Three patients demonstrated positive uptake at the primary site later confirmed by biopsy and at surgery as residual disease. Two patients with negative scans each demonstrated complete pathologic response. In 5 patients with medullary thyroid cancer, 64Cu-DOTA-hT84.66-M5A identified disease not seen on initial CT scans in 3 patients, later confirmed to be disease by subsequent surgery or MRI. Conclusions: 64Cu-DOTA-hT84.66-M5A demonstrates promise in tumor detection, particularly in patients with locally advanced rectal cancer and medullary thyroid cancer. A successor trial in locally advanced rectal cancer has been initiated to further evaluate this agent's ability to define tumor extent before and assess disease response after neoadjuvant chemotherapy and radiotherapy. clinical trial.gov (NCT02293954).

Long-term follow up of patients with hematological malignancies treated with total body irradiation using intensity modulated radiation therapy.

Background: With the advent of modern radiation treatment technologies such as intensity modulated radiation therapy (IMRT), there has been increasing interest in its use for total body irradiation (TBI) conditioning regimens for hematopoietic cell transplantation (HCT) to achieve lower doses to critical organs such as the lungs and kidneys. Although this has been reported on in early studies, long-term safety and efficacy data is limited. Methods: We performed a single institution matched-pair retrospective analysis of patients treated with IMRT TBI and standard TBI between 2010 and 2020 to provide data on long-term outcomes. Patients with hematologic malignancies, who could not tolerate standing for traditional TBI or who received prior radiation received IMRT TBI. Patients were matched based on age, diagnosis, disease status, and year of transplant, and were matched 2:1 to the standard TBI and IMRT TBI cohorts. Patient and treatment characteristics, toxicity, graft-versus-host disease (GVHD), dosimetry, and outcomes were evaluated for each cohort. Results: A total of 13 patients met inclusion criteria for the IMRT cohort, leading to 26 patients in the standard TBI cohort. There was no significant difference in relevant clinical factors between the cohorts. Reasons for using IMRT over conventional TBI included being unable to stand (n=5), prior radiation (n=5), and pediatric patient requiring anesthesia (n=3). Among living patients, median follow-up for all patients was 5.1 years in the IMRT TBI cohort and 5.5 years in the standard TBI cohort. The 5-yr estimate of OS was 68% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.706). The 5-yr estimate of RFS was 54% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.529). There was no clinically significant pneumonitis, nephritis, hypothyroidism, or cataracts reported in the IMRT TBI cohort. 41.7% of patients in the IMRT TBI cohort and 79.2% of patients in the standard TBI cohort experienced Grade II-IV acute GVHD (p=0.023). Conclusions: IMRT TBI appears to lead to favorable long-term outcome and dosimetry, and therefore potentially improved long-term toxicity profile compared to conventional TBI. IMRT TBI warrants further investigation as part of larger prospective trials.

Total marrow irradiation reduces organ damage and enhances tissue repair with the potential to increase the targeted dose of bone marrow in both young and old mice.

Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment. Whether such dose escalation is feasible in elderly patients, and how the organ toxicity profile changes when switching to TMI in patients of all ages are critical questions that need to be addressed. We used our recently developed 3D image-guided preclinical TMI model and evaluated the radiation damage and its repair in key dose-limiting organs in young (~8 weeks) and old (~90 weeks) mice undergoing congenic bone marrow transplant (BMT). Engraftment was similar in both TMI and TBI-treated young and old mice. Dose escalation using TMI (12 to 16 Gy in two fractions) was well tolerated in mice of both age groups (90% survival ~12 Weeks post-BMT). In contrast, TBI at the higher dose of 16 Gy was particularly lethal in younger mice (0% survival ~2 weeks post-BMT) while old mice showed much more tolerance (75% survival ~13 weeks post-BMT) suggesting higher radio-resistance in aged organs. Histopathology confirmed worse acute and chronic organ damage in mice treated with TBI than TMI. As the damage was alleviated, the repair processes were augmented in the TMI-treated mice over TBI as measured by average villus height and a reduced ratio of relative mRNA levels of amphiregulin/epidermal growth factor (areg/egf). These findings suggest that organ sparing using TMI does not limit donor engraftment but significantly reduces normal tissue damage and preserves repair capacity with the potential for dose escalation in elderly patients.

Role of radiotherapy in treatment of extramedullary relapse following total marrow and lymphoid irradiation in high-risk and/or relapsed/refractory acute leukemia.

Background: Total Marrow and Lymphoid Irradiation (TMLI) is a promising component of the preparative regimen for hematopoietic cell transplantation in patients with high-risk acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Extramedullary (EM) relapse after TMLI is comparable to TBI and non-TBI conditioning regimens. This study evaluates outcomes of patients treated with radiotherapy (RT) with EM relapse previously treated with TMLI. Methods: A retrospective analysis of five prospective TMLI trials was performed. TMLI targeted bones and major lymphoid tissues using image-guided tomotherapy, with total dose ranging from 12 to 20 Gy. EM recurrences were treated at the discretion of the hematologist and radiation oncologist using RT ± chemotherapy. Descriptive statistics and survival analysis were then performed on this cohort. Results: In total, 254 patients with refractory or relapsed AML or ALL were treated with TMLI at our institution. Twenty-one patients were identified as receiving at least one subsequent course of radiation. A total of 67 relapse sites (median=2 sites/patient, range=1-16) were treated. Eleven relapsed patients were initially treated with curative intent. Following the initial course of subsequent RT, 1-year, 3-year and 5-year estimates of OS were 47.6%, 32.7% and 16.3%, respectively. OS was significantly better in patients treated with curative intent, with median OS of 50.7 months vs 1.6 months (p<0.001). 1-year, 3-year and 5-year estimates of PFS were 23.8%, 14.3% and 14.3%, respectively. PFS was significantly better in patients treated with curative intent, with median PFS of 6.6 months vs 1.3 months (p<0.001). Following RT, 86.6% of the sites had durable local control. Conclusions: RT is an effective modality to treat EM relapse in patients with acute leukemia who relapse after HCT achieving high levels of local control. In patients with limited relapse amenable to curative intent, radiation confers favorable long-term survival. Radiation as salvage treatment for EM relapse after HCT warrants further evaluation.

Oligometastatic Breast Cancer Patients Treated with High-Dose Chemotherapy and Targeted Radiation: Long-Term Follow-Up of a Phase II Trial.

BACKGROUND: Patients with oligometastatic breast cancer (oMBC) may benefit from aggressive local therapy. We sought to assess the effects of consolidative radiation therapy (RT) on outcomes in oMBC patients treated on a prospective phase II trial of high-dose chemotherapy (HDCT). METHODS: Between 2005 and 2009, 12 patients with oMBC (≤3 metastatic sites) cancer were treated on protocol. Patients were to receive tandem HDCT supported by hematopoietic cell rescue (HCR). All radiographically identifiable oligometastatic sites received targeted radiation. RESULTS: HDCT was initiated at a median of 6.7 (3.5-12.7) months after diagnosis of oMBC. Hormone receptors (HR) were positive in 91.6% of patients, and HER2 was overexpressed in 25% of patients. Median radiation dose (EQD2) was 41.2 (37.9-48.7) Gy. Median follow-up was 13.1 (6.8-15.1) years for living patients. Ten-year PFS and OS were 33% (95%CI, 10-59%) and 55% (95%CI, 22-79%), respectively. Durable local control of treated lesions was 87.5%. At the last follow up, two patients remained progression free and two more were without evidence of disease following additional salvage treatment. CONCLUSIONS: Although modern systemic therapies have obviated the use of HDC, aggressive local therapy warrants further evaluation and fractionated radiotherapy is a viable alternative if SBRT is not available.

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review.

Purpose: TMI utilizes IMRT to deliver organ sparing targeted radiotherapy in patients undergoing hematopoietic cell transplantation (HCT). TMI addresses an unmet need, specifically patients with refractory or relapsed (R/R) hematologic malignancies who have poor outcomes with standard HCT regimens and where attempts to improve outcomes by adding or dose escalating TBI are not possible due to increased toxicities. Over 500 patients have received TMI at this center. This review summarizes this experience including planning and delivery, clinical results, and future directions. Methods: Patients were treated on prospective allogeneic HCT trials using helical tomographic or VMAT IMRT delivery. Target structures included the bone/marrow only (TMI), or the addition of lymph nodes, and spleen (total marrow and lymphoid irradiation, TMLI). Total dose ranged from 12 to 20 Gy at 1.5-2.0 Gy fractions twice daily. Results: Trials demonstrate engraftment in all patients and a low incidence of radiation related toxicities and extramedullary relapses. In R/R acute leukemia TMLI 20 Gy, etoposide, and cyclophosphamide (Cy) results in a 1-year non-relapse mortality (NRM) rate of 6% and 2-year overall survival (OS) of 48%; TMLI 12 Gy added to fludarabine (flu) and melphalan (mel) in older patients (≥ 60 years old) results in a NRM rate of 33% comparable to flu/mel alone, and 5-year OS of 42%; and TMLI 20 Gy/flu/Cy and post-transplant Cy (PTCy) in haplo-identical HCT results in a 2-year NRM rate of 13% and 1-year OS of 83%. In AML in complete remission, TMLI 20 Gy and PTCy results in 2-year NRM, OS, and GVHD free/relapse-free survival (GRFS) rates of 0%, 86·7%, and 59.3%, respectively. Conclusion: TMI/TMLI shows significant promise, low NRM rates, the ability to offer myeloablative radiation containing regimens to older patients, the ability to dose escalate, and response and survival rates that compare favorably to published results. Collaboration between radiation oncology and hematology is key to successful implementation. TMI/TMLI represents a paradigm shift from TBI towards novel strategies to integrate a safer and more effective target-specific radiation therapy into HCT conditioning beyond what is possible with TBI and will help expand and redefine the role of radiotherapy in HCT.

Risk of Subsequent Malignant Neoplasms Following Hematopoietic Stem Cell Transplantation with Total Body Irradiation or Total Marrow Irradiation: Insights from Early Follow-Up.

Total marrow irradiation (TMI) is an alternative to total body irradiation (TBI) as a component of the conditioning regimen for hematopoietic cell transplantation (HCT), offering the ability to deliver more targeted doses and facilitating organ-sparing. The organ-sparing effect of TMI is theorized to decrease the risk of complications associated with radiation, including subsequent malignant neoplasms (SMNs), while allowing for dosage escalation to improve oncologic outcomes. The purpose of this study was to compare SMNs rates among patients treated with TBI- or TMI-based conditioning regimens. We hypothesized that TMI would yield a rate of SMNs comparable to, if not lower than, TBI. A retrospective matched-pair analysis of patients who underwent allogeneic HCT and received either TBI- or TMI-based conditioning regimens to a total dose of 12 to 20 Gy was performed. A total of 171 patients received TMI-based conditioning and 171 received TBI-based conditioning, matched based on age, sex, diagnosis, and length of follow-up. SMNs were identified from an established long-term follow-up protocol, our institutional cancer registry, and the California Cancer Registry. There were no significant differences in patient and clinical characteristics between the TMI and TBI cohorts except for clinical response status at transplantation and radiation dose. As expected, patients in the TMI received higher radiation doses (median dose, 16.0 Gy for the TMI cohort versus 13.2 Gy for the TBI cohort; P < .001). The median follow-up for both cohorts was 2.0 years (range, .5 to 12.3 years). There was no significant difference in the risk of developing SMNs between the 2 cohorts (P = .81). A total of 9 patients (5.3%) conditioned with TBI and 10 patients (5.8%) conditioned with TMI developed SMNs, at a median of 3.3 years and 1.7 years following HCT, respectively. Excluding nonmelanoma skin cancers and noninvasive neoplasms, 2 patients in the TBI cohort developed SMNs (both melanomas), and 1 patient in the TMI cohort developed an SMN (colon cancer). No patients developed a subsequent hematologic malignancy. TMI-based conditioning is not associated with a significant difference in the risk of developing SMNs compared with TBI-based conditioning during early post-HCT follow-up. Future studies with longer follow-up may be needed to further characterize the risk of SMNs associated with TMI-based conditioning regimens compared with TBI-based regimens.

Long-Term Outcomes of Patients on a Phase II Prospective Trial of Oligometastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation and External Beam Radiation.

PURPOSE: External beam radiation therapy (EBRT) to oligometastases may improve outcomes in patients with oligometastatic hormone-sensitive prostate cancer (oHSPC). Follow-up on this cohort has been limited to <5 years and prospective data on de novo patients with oHSPC are lacking. We reviewed the long-term outcomes of patients with oHSPC treated with EBRT and androgen deprivation therapy on a prospective trial. METHODS AND MATERIALS: From 2006 to 2011, patients with oHSPC with 1 to 5 metastases received 36 weeks of androgen deprivation therapy (luteinizing hormone-releasing hormone agonist + bicalutamide) and up to 53 Gy to all visible metastases. When indicated, the primary tumor or prostate bed was treated with EBRT up to 78 or 66 Gy, respectively. RESULTS: Twenty-nine patients were treated: 15 de novo, 14 oligorecurrent, and 21 patients (72.4%) had bone metastases. Median number of metastases per patient was 1 (range, 1-5). EBRT was administered to 52 lesions (38 bone, 12 pelvic lymph nodes [LNs], 2 nonpelvic LNs) up to 53 Gy (range, 47-66). Median follow-up was 9.9 years (years; range, 0.2-14.4). Median overall survival was 9.7 years (95% confidence interval [CI], 5.8-not reached). Median progression-free survival was 1.9 years (95% CI, 1.6-2.2). Patients who presented with prostate cancer-defined de novo metastases had significantly improved (P = .04) median progression-free survival (2.0 years; 95% CI, 1.3-6.0) compared with oligorecurrent patients (1.8 years; 95% CI, 1.0-2.0). Patients who presented with LN-only metastases had numerically improved (P = .13) median PFS (5.8 years; 95% CI, 1.2-not reached) compared with patients with bony metastases (1.8 years; 95% CI, 1.3-2.0). At last follow-up, 17 patients (58.6%) had local control of all EBRT-treated metastases. The metastases that locally progressed had previously been controlled for median 3.5 years (range, 1.7-10.5). CONCLUSIONS: Our results compare favorably with other reported studies of patients with oHSPC and provide new insights into their long-term outcomes.

Total Marrow and Lymphoid Irradiation with Post-Transplantation Cyclophosphamide for Patients with AML in Remission.

Graft-versus-host disease (GVHD) has remained the main cause of post-transplantation mortality and morbidity after allogeneic hematopoietic cell transplantation (alloHCT), adding significant economic burden and affecting quality of life. It would be desirable to reduce the rate of GVHD among patients in complete remission (CR) without increasing the risk of relapse. In this study, we have tested a novel conditioning regimen of total marrow and lymphoid irradiation (TMLI) at 2000 cGy, together with post-transplantation cyclophosphamide (PTCy) for patients with acute myeloid leukemia in first or second CR, to attenuate the risk of chronic GVHD by using PTCy, while using escalated targeted radiation conditioning before allografting to offset the possible increased risk of relapse. The primary objective was to evaluate the safety/feasibility of combining a TMLI transplantation conditioning regimen with a PTCy-based GVHD prophylaxis strategy, through the assessment of adverse events in terms of type, frequency, severity, attribution, time course, duration, and complications, including acute GVHD, infection, and delayed neutrophil/platelet engraftment. Secondary objectives included estimation of non-relapse mortality (NRM), overall survival (OS), relapse-free survival, acute and chronic GVHD, and GVHD-relapse-free survival (GRFS). A patient safety lead-in was first conducted to ensure there were no unexpected toxicities and was expanded on the basis of lack of dose-limiting toxicities. The patient safety lead-in segment followed 3 + 3 dose expansion/(de-)escalation rules based on observed toxicity through day 30; the starting dose of TMLI was 2000 cGy, and a de-escalation to 1800 cGy was considered. After the safety lead-in segment, an expansion cohort of up to 12 additional patients was to be studied. TMLI was administered on days -4 to 0, delivered in 200 cGy fractions twice daily. The radiation dose delivered to the liver and brain was kept at 1200 cGy. Cyclophosphamide was given on days 3 and 4 after alloHCT, 50 mg/kg each day for GVHD prevention; tacrolimus was given until day 90 and then tapered. Among 18 patients with a median age of 40 years (range 19-56), the highest grade toxicities were grade 2 Bearman bladder toxicity and stomatitis. No grade 3 or 4 Bearman toxicities or toxicity-related deaths were observed. The cumulative incidence of acute GVHD grade 2 to 4 and moderate-to-severe chronic GVHD were 11.1% and 11.9%, respectively. At a median follow up of 24.5 months, two-year estimates of OS and relapse-free survival were 86.7% and 83.3%, respectively. Disease relapse at 2 years was 16.7%. The estimates of NRM at 2 years was 0%. The GVHD/GRFS rate at 2 years was 59.3% (95% confidence interval, 28.8-80.3). This chemotherapy-free conditioning regimen, together with PTCy and tacrolimus, is safe, with no NRM. Preliminary results suggest an improved GRFS rate.

Role of Salvage Radiation Treatment of Relapses in Relapsed/Refractory Diffuse Large B Cell Lymphoma Post-Autologous Stem Cell Transplant.

PURPOSE: Approximately 50% of patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) will relapse post-autologous stem cell transplant (ASCT), and the role of salvage therapy is not well defined. We examined radiation therapy (RT) as salvage treatment in this patient population. MATERIALS AND METHODS: A retrospective review of patients with DLBCL who had an ASCT during 2004 to 2016 and subsequently relapsed was performed. Clinical and pathologic characteristics were collected, including detailed information regarding post-ASCT treatment. Response rates were tabulated and survival analysis was performed, stratified by salvage modality. RESULTS: A total of 165 patients with R/R DLBCL who relapsed after ASCT were identified; 91 of these patients received salvage chemotherapy as their first line of relapse therapy, and 14 received salvage radiation. Median salvage RT dose was 36 Gy (range, 24-50). The objective response rate with salvage chemotherapy and RT was 53.0% and 78.5%, respectively (P = 0.07), and the complete response rate was 31.3% and 57.1%, respectively (P = 0.06). Median follow-up among living patients was 48.9 months (range, 4.8-136.17). Among patients with one site of relapse post-ASCT, median overall survival in patients who received salvage RT was significantly improved (P = 0.008) relative to chemotherapy (not reached [95% confidence interval {CI}, 8.4-not reached] versus 10.0 months [95% CI, 5.3-17.8]). Median progression-free survival in patients who received salvage RT was not significantly different (P = 0.16) relative to chemotherapy (8.4 months [95% CI, 2.5-47.7] versus 3.9 months [95% CI, 2.4-8.5]). CONCLUSIONS: Patients who received RT as first salvage therapy post-ASCT, particularly with localized disease, had favorable oncologic outcomes. Future studies are needed to understand which patients with R/R DLBCL who relapse after ASCT may benefit from early salvage RT versus chemotherapy.

Prostate Cancer Characteristics and Outcomes after Prostatectomy in Asian-American Men.

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in American men, with striking differences between ethnic groups. Given the potential for lifestyle or genetic variations between subsets of Asian-American men to impact prostate cancer behavior, we sought to define the outcomes after radical prostatectomy among various Asian groups treated at an NCI-designated comprehensive cancer center. METHODS: The City of Hope IRB-approved prostatectomy database was searched from 2003 to 2015 to identify Asian-American men. Clinical and pathologic features were collected and analyzed for association with biochemical recurrence-free survival and overall survival (OS). Categorical data were evaluated using χ2and Fisher's exact tests. Survival curves were compared between groups using log-rank testing. RESULTS: Three hundred and eighty-three Asian-American men were included in the dataset. While Asian men as a group had lower BMI than African-American and white men in the database, there was a wide range between ethnic sub-groups. Chinese men more commonly presented with D'Amico low risk disease features (P= .04) compared to other Asian men. Pacific Islander men had the lowest rate of ≥T3 stage and the highest biochemical recurrence-free survival. OS for Chinese men was better than for all Asian patients combined (P= .046). After controlling for D'Amico risk and in multivariate analysis, Chinese men still had improved OS than other Asian men after prostatectomy (P= .03). CONCLUSIONS: Asian-American men have differing prostate cancer characteristics. Future efforts to delineate and impact upon prostate cancer outcomes should categorize Asian men by subgroup in order to better elucidate biology, lifestyle factors and/or treatment preferences that may contribute to observed differences.