Received Salvage Chemotherapy Research Articles

Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry

AbstractOptimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHLs) is unknown. In this population-based study, outcomes in R/R peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-positive (ALK+) and ALK-negative (ALK–) anaplastic large cell lymphoma (ALCL) were evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL, and ALK– ALCL (≥18 years) diagnosed in 2014 to 2019 were identified using the Netherlands Cancer Registry. End points were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% received salvage chemotherapy, 20% received brentuximab vedotin (BV), and 36% received other treatment. In third-line treatment, BV was most commonly used (38%). ORR after second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. The risk of second relapse was negatively affected by early relapse (<12 months after diagnosis), whereas BV reduced this risk compared with salvage chemotherapy. Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for patients with R/R T-NHL treated with BV compared with patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for patients with R/R T-NHL is challenged.

The outcome of relapsed childhood acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantations: A single-center experience.

In children with high-risk childhood acute leukemia who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT), relapse is still the leading cause of treatment failure. The prognosis is poor, yet prospective studies have only limited data on risk factors and outcomes. We aimed to understand the outcomes and prognostic factors for patients with acute lymphoblastic leukemia (ALL) who relapsed following allo-HSCT. We analyzed retrospectively 46 children with childhood acute lymphoblastic leukemia who had relapsed after receiving their first alloHSCT. All these patients received salvage chemotherapy which consisted of fludarabine, cytarabine, and idarubicin before performing a second alloHSCT. The median follow-up of the 46 patients after the first transplantation was 366 days. The median time from first allo-HSCT to relapse was 278.4±238.4 days. Forty-six patients received salvage chemotherapy before the second alloHSCT, and CR was achieved in 32 of 46 patients. However, only 17 (37%) of 46 patients received a second allo-HSCT, and 15 of 46 patients died from disease progression, infections, and bleeding. Twelve patients are still alive after the second allo-HSCT. Two-year overall survival (OS) was 38.9%. Local therapy was given to 10 (21.8%) patients, either as part of systemic therapy or alone. In multivariate analyses, the time of relapse and curative salvage therapy with a second allo-HSCT were identified as significant prognostic factors for OS. Children with leukemia who had relapsed after the first allo-HSCT received salvage chemotherapy. Our statistical analysis showed that the second HSCT could be beneficial for outcomes if patients relapsed beyond 180 days of the first allo-HSCT.

Abstract CT029: Chemotherapy-free neoadjuvant regimen with durvalumab, trastuzumab and pertuzumab (DTP) in HER2-enriched early breast cancer: A prospective, open-label phase II trial

Abstract Background: High risk HER2-positive early breast cancer (EBC) patients are traditionally treated with neoadjuvant chemotherapy in combination with HER2-directed therapy. De-escalation approaches are being studied as benefits of chemotherapy in the HER2-enriched subset of EBC, but they have been inconclusive thus far. Preclinical studies suggest synergistic effect of immune checkpoint blockade (ICB) and HER2-directed therapy. This study hypothesizes that biologically directed HER-2 targeted therapy with Trastuzumab (T) and Pertuzumab (P) together with ICB (Durvalumab, D) will obviate the need of chemotherapy in HER2-enriched EBC patients. Methods: In this single arm, open-label phase II study, previously untreated, stage I-III, ER/PR negative, HER2-enriched breast cancer (BluePrint®, Agendia) patients were treated with D (1120mg IV, q3w), T (8mg/kg IV loading dose, 6 mg/kg IV q3w), and P (840 mg IV loading dose, 420 mg IV q3w) for 6 cycles. Response was assessed at end of 6 cycles with breast MRI and possible biopsy if residual disease was present. Responders (MRI and/or biopsy negative for residual cancer) proceeded to surgery, while patients with biopsy-proven residual disease were offered salvage standard chemotherapy (TCHP) before surgery. Primary end-point was pathological response rate defined as residual cancer burden (RCB)-0 and RCB-1. Patients who achieved RCB 0/1 received adjuvant DTP for 1 year. Results: A total of 51 patients were screened; 39 patients have been enrolled and received at least one cycle of treatment. Of these, 35 patients are evaluable for pathologic response, and 2 patients are still receiving treatment. One patient died of unrelated myocardial infarction, and one patient was lost to follow-up. The median age was 55 years (range 29-85). Thirty-one (79.5%) patients were white; 4 (10.3%) African American, and 4 (10.3%) Asian. Twenty-nine (74.3%) patients had &amp;gt;=T2 tumors; 21 (53.8%) patients had N1/N2/N3 disease. Six patients (15.3%) had biopsy-proven residual disease after DTP therapy, and they received salvage standard neoadjuvant TCHP chemotherapy. The combination was well tolerated; 5 (18.8%) patients had G3-4 adverse events. Twenty-seven of thirty-five patients (77.1%) had pathologic RCB 0/1 (RCB0, 20/35; RCB1 7/35), of whom only 3 patients had received salvage chemotherapy. Correlative studies, including tumor-infiltrating lymphocytes, immune-related gene signatures and PD-L1 expression are underway. Conclusions: Chemotherapy-free neoadjuvant regimen with DTP in HER2-enriched EBC showed high pathologic response rates comparable to that with chemotherapy. This DTP regimen may provide an effective, relatively non-toxic, and biologically driven alternative to standard of care chemotherapy in this HER2-enriched subset of EBC. Citation Format: Jian Guan, Kai Sun, Dharamvir Jain, Sunil Mathur, Hanh Mai, Polly Niravath, Jenny Chang. Chemotherapy-free neoadjuvant regimen with durvalumab, trastuzumab and pertuzumab (DTP) in HER2-enriched early breast cancer: A prospective, open-label phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT029.

Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial

Whether high-dose cytarabine-based salvage chemotherapy, administered to induce complete remission in patients with poor responsive or relapsed acute myeloid leukaemia scheduled for allogeneic haematopoietic stem-cell transplantation (HSCT) after intensive conditioning confers a survival advantage, is unclear. To test salvage chemotherapy before allogeneic HSCT, patients aged between 18 and 75 years with non-favourable-risk acute myeloid leukaemia not in complete remission after first induction or untreated first relapse were randomly assigned 1:1 to remission induction with high-dose cytarabine (3 g/m2 intravenously, 1 g/m2 intravenously for patients >60 years or with a substantial comorbidity) twice daily on days 1-3 plus mitoxantrone (10 mg/m2 intravenously) on days 3-5 or immediate allogeneic HSCT for the disease control group. Block randomisation with variable block lengths was used and patients were stratified by age, acute myeloid leukaemia risk, and disease status. The study was open label. The primary endpoint was treatment success, defined as complete remission on day 56 after allogeneic HSCT, with the aim to show non-inferiority for disease control compared with remission induction with a non-inferiority-margin of 5% and one-sided type 1 error of 2·5%. The primary endpoint was analysed in both the intention-to-treat (ITT) population and in the per-protocol population. The trial is completed and was registered at ClinicalTrials.gov, NCT02461537. 281 patients were enrolled between Sept 17, 2015, and Jan 12, 2022. Of 140 patients randomly assigned to disease control, 135 (96%) proceeded to allogeneic HSCT, 97 (69%) after watchful waiting only. Of 141 patients randomly assigned to remission induction, 134 (95%) received salvage chemotherapy and 128 (91%) patients subsequently proceeded to allogeneic HSCT. In the ITT population, treatment success was observed in 116 (83%) of 140 patients in the disease control group versus 112 (79%) of 141 patients with remission induction (test for non-inferiority, p=0·036). Among per-protocol treated patients, treatment success was observed in 116 (84%) of 138 patients with disease control versus 109 (81%) of 134 patients in the remission induction group (test for non-inferiority, p=0·047). The difference in treatment success between disease control and remission induction was estimated as 3·4% (95% CI -5·8 to 12·6) for the ITT population and 2·7% (-6·3 to 11·8) for the per-protocol population. Fewer patients with disease control compared with remission induction had non-haematological adverse events grade 3 or worse (30 [21%] of 140 patients vs 86 [61%] of 141 patients, χ2 test p<0·0001). Between randomisation and the start of conditioning, with disease control two patients died from progressive acute myeloid leukaemia and zero from treatment-related complications, and with remission induction two patients died from progressive acute myeloid leukaemia and two from treatment-related complications. Between randomisation and allogeneic HSCT, patients with disease control spent a median of 27 days less in hospital than those with remission induction, ie, the median time in hospital was 15 days (range 7-64) versus 42 days (27-121, U test p<0·0001), respectively. Non-inferiority of disease control could not be shown at the 2·5% significance level. The rate of treatment success was also not statistically better for patients with remission induction. Watchful waiting and immediate transplantation could be an alternative for fit patients with poor response or relapsed acute myeloid leukaemia who have a stem cell donor available. More randomised controlled intention-to-transplant trials are needed to define the optimal treatment before transplantation for patients with active acute myeloid leukaemia. DKMS and the Gert and Susanna Mayer Stiftung Foundation.

Validation of Combs prognostic scoring system in Indian recurrent glioma patients treated with re-radiation.

Retrospective audit of recurrent glioma patients treated by different fractionation schedules and to validate the modified Combs prognostic score in Indian patient cohort. Between Jan 2009 and June 2022, 66 recurrent gliomas patients treated with standard adjuvant treatment-radiation (RT) ± temozolomide (chemotherapy)-and re-treated with RT (±chemotherapy) were categorized as per modified Combs prognostic criteria and outcomes were compared. Sixty-six patients with recurrent gliomas who received reirradiation (re-RT) were audited-53% males; 61% Karnofsky performance status (KPS) ≥80 at time of re-RT; median age 41.5 years (range, 6 to 70 years); 67% <50 years; primary histology low-grade glioma in 33% ; grade III 27%, grade IV 40%; initial median dose of 60 Gy equivalent dose in 2 Gy fractions EQD2; maximum safe resection at recurrence 41%; mean and median follow-up 78 ± 51 months and 66 months. Mean time interval between RT was 46.4 ± 39 months. Mean planning target volume (PTV) volume in conventional RT (Conv-RT), hypofractionated RT (Hypo-RT), and ultra-hypofractionated RT (UF-RT) was 226.1 ± 140.7 mL, 162.8 ± 123.3 mL, and 143.3 ± 145.8 mL. Mean dose for Conv-RT, Hypo-RT, and UF-RT was 50 Gy (range, 40 to 60), 31 Gy (range, 20 to 40), and 20 Gy (range, 10 to 30). Mean overall survival (OS) in Conv-RT, Hypo-RT, and UF-RT cohort was 18.8 months (range, 2.4 to 76.8); 6.6 months (range, 2 to 17.4), and 13.9 months (range, 3 to 131.9). Median OS as per Combs criteria were 16.6 months (Group a), 24.6 months (Group b), 4.6 months (Group c), and 3 months (Group d). Significant survival benefit was with good KPS score (KPS >80 vs. <80; 20.46 vs. 5.25 months; p < 0.001), patients receiving salvage chemotherapy (20.46 vs. 6.96 months; p = 0.001), and patients received re-RT biological equivalent dose BED3 >80 Gy (16.62 vs. 5.48 months; p = 0.03). Median OS in our patient cohort and Combs cohort in Group a was 16.6 and 19.5 months; Group b was 24.6 and 11.3 months; Group c was 4.7 and 8.1 months, and Group d was 2 and 5.5 months, respectively. Six months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 100%, 92%, 34%, 17% and 94%, 79%, 70%, 41%, respectively. Twelve months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 88%, 74%, 22%, 0% and 88%, 47%, 22%, 7%, respectively. Modified Combs prognostic factors predicts OS and is applicable in Indian subcontinent patient population.

The Impact of 131I-Metaiodobenzylguanidine as a Conditioning Regimen of Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Neuroblastoma.

The optimal conditioning regimen of tandem high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for high-risk neuroblastoma (HR-NBL) has not been established. The efficacy of 131I-MIBG therapy is under exploration in newly diagnosed HR-NBL patients. Here, we compared the outcomes of tandem HDC/ASCT between the 131I-MIBG combination and non-MIBG groups. We retrospectively analyzed the clinical data of 33 HR-NBL patients who underwent tandem HDC/ASCT between 2007 and 2021 at the Seoul National University Children's Hospital. The median age at diagnosis was 3.6 years. 131I-MIBG was administered to 13 (39.4%) of the patients. Thirty patients (90.9%) received maintenance therapy after tandem HDC/ASCT, twenty-two were treated with isotretinoin ± interleukin-2, and eight received salvage chemotherapy. The five-year overall survival (OS) and event-free survival (EFS) rates of all patients were 80.4% and 69.4%, respectively. Comparing the 131I-MIBG combined group and other groups, the five-year OS rates were 82.1% and 79.7% (p = 0.655), and the five-year EFS rates were 69.2% and 69.6% (p = 0.922), respectively. Among the adverse effects of grade 3 or 4, the incidence of liver enzyme elevation was significantly higher in the non-131I-MIBG group. Although tandem HDC/ASCT showed promising outcomes, the 131I-MIBG combination did not improve survival rates.

Outcomes in Patients with Relapsed Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Treated with CAR-T Cell Therapies or Salvage Chemotherapy - a Single-Institution Experience

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of large B-cell lymphoma. A substantial subset of THRLBCL patients (pts) relapse after frontline anthracycline-based therapy. There is a scarcity of outcome data on therapy options for relapsed/refractory (r/r)THRLBCL, particularly CD19 CAR-T therapy.A recent genetic and spatial analysis provided critical insights into the complex interactions at the tumor-immune interface in THRLBCL. Understanding the mechanisms by which tumor cells evade the immune system is crucial in designing treatment strategies. This retrospective study aims to analyze clinicopathologic data in pts with r/r THRLBCL with the goal of identifying patterns that may influence response rates and long-term survival. METHODS: Pts who were evaluated and treated at MD Anderson Cancer Center (MDACC) with THRLBCL from 1/2005-5/2023 were included in the analysis. We reviewed demographic, clinical and pathological characteristics, treatments, and outcomes through an approved IRB protocol. We excluded cases with ambiguous diagnosis (such as DLBCL with increased infiltrate of T-cells and/or histiocytes), missing treatment, and/or no follow up information. Progression-free survival (PFS) and overall survival (OS) were calculated from start of treatment until progression or death using Kaplan-Meier. Log-rank test was used to evaluate the difference between pt groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for all analyses. RESULTS: A total of 212 pts were reviewed, and we excluded 86 pts who did not meet selection criteria. Out of 126 pts, 63 with biopsy-confirmed relapse after 1st line chemoimmunotherapy were included in the analysis (Table-1). The median age was 49 (20-79 years); and 49 pts (78%) were males. Twenty-one (34%) pts had documented NLPHL at the time of or predating the THRLBCL diagnosis. At relapse, 93 % had advance stage disease (stage 3 and 4). Splenic involvement was documented in 57% and 80% of pts had one or more sites of extra nodal disease. Most pts who relapsed received front line RCHOP (77%) or R-EPOCH (11%). Twenty-six pts (41%) had primary refractory disease, and 24 pts (38%) relapsed within 12 months. The median time to progression from 1st line treatment was 7.4 months(2.2~145.9 months). The most common 2 nd line therapy was salvage chemotherapy (82%) such as R-ICE (n=41), R-DHAP(n=4), R-GemOx (n=3). Overall response rate (ORR) to 2 nd line salvage chemotherapy was 75% with CR of 57%. For pts who received 2nd line salvage chemotherapy with the intent to undergo HSCT, the PFS at 2 years was 53% (95% CI: 0.4-0.68, p&amp;lt; 0.0001) and OS was 64% (95% CI: 0.5- 0.8, p&amp;lt; 0.372). Among pts who received consolidation with HSCT, (n=30, 57%), 5 pts relapsed at the time of last follow up.With a median follow-up time of 60.1 months (95% CI: 33.6~90.3 months), the median PFS from all 2nd line treatments was 11 months (95% CI: 4.7 ~ NA ) and for pts who received salvage chemotherapy with HSCT intent was 50.26 (95% CI: 7 ~ NA months). The median OS from 2nd line for all pts was 77.3 months (95% CI: 22.2 ~ NA months) and for pts who received salvage chemotherapy with HSCT intent OS was not reached (95% CI: 32 ~ NA months). Among 11 pts who received 3 rd line salvage chemotherapy, the median PFS was 2 months, and only one pt received HSCT. All pts eventually had progressive disease. Eleven pts received CD19 CAR-T (Axi-cel-9, Liso-cel-2),(table-1) 6 pts received as 2 nd line, 4 received as 3rd line and 1 pt received as 4 th line. Best ORR to CAR-T at any lines was 45% with CR of 36.4%. At a median follow-up time of 12.3 months (95% CI: 2.4 ~ NA months), all but one pt had disease progression. Median PFS was 1.7 months (95% CI: 1.1 ~ NA months). 6-month PFS was 21% (Figure 1). One pt who had response experienced prolonged remission of 17 months before relapsing. CONCLUSION: Our study highlights the unique biology and poorer prognosis of TCHRBCL compared to other DLBCL subtypes. Despite the success of CD19 CAR-T therapy in DLBCL, TCHRBCL pts have shown limited response to these therapies, demonstrating the challenges of achieving long-term remission in this group. Our study shows the high unmet need for improved therapies that can target the unique biology in TCHRBCL. We plan to report a comparative spatial analysis evaluating the tumor-immune interface that can contribute to resistance to Immune effector cell therapies at the meeting.

Incidence and Risk Factors for Central Nervous System Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia

Background Acute lymphoblastic leukemia (ALL) is frequently accompanied with the involvement of the central nervous system (CNS). The clinical prognosis for ALL patients with CNS disease is generally unfavorable, and prophylactic measures such as intrathecal chemotherapy are highly recommended. In adult ALL patients, hematopoietic stem cell transplantation (HSCT) presents a potential curative approach. However, there are currently only a few reports available on the risk factors and epidemiology of CNS relapse after HSCT. Method We conducted a retrospective single-center cohort study involving 1043 patients diagnosed with either acute lymphoblastic leukemia (ALL) or mixed phenotype acute leukemia (MPAL). These patients were treated at our center using the same treatment protocol between 2009 and 2022. During the remission induction phase, we utilized a modified hyper-CVAD regimen, along with six rounds of prophylactic intrathecal (IT) chemotherapy. High-risk patients who had suitable donors underwent allogeneic hematopoietic stem cell transplantation (HSCT) as part of their post-remission therapy. Diagnosis of central nervous system (CNS) leukemia was established when neurologic symptoms were observed in correlation with CNS lesions on imaging studies, or when leukemic blasts were detected in the cerebrospinal fluid (CSF). In our study, we examined the incidence, risk factors, and survival outcomes of patients who experienced CNS relapse after transplantation. Results Among the entire cohort of 1043 patients, CNS involvement was observed in 3 (0.3%) patients at initial diagnosis and 12 (1.2%) during chemotherapy. We proceeded with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 755 consecutive patients. Among these 755 patients, 3 had CNS leukemia prior to transplantation. Among the group of 755 patients, a total of 224 (29.6%) experienced relapse. Of these relapses, 142 (18.8%) were bone marrow relapses alone, 54 (7.1%) were extramedullary relapses alone (with CNS involvement in 21 [38.8%]), and 28 (3.7%) had both bone marrow and extramedullary relapses (with CNS involvement in 13 [46.4%]). Overall, extramedullary relapse was observed in 82 (10.8%) patients, with CNS involvement in 34 (4.5%) cases, following allo-HSCT. The 5-year cumulative incidence of CNS relapse was 4.6%, which was significantly higher in patients with Philadelphia chromosome-positive (Ph-positive) ALL (9.4% vs. 1.0%, p &amp;lt;0.001), as well as those with a high leukocyte count at diagnosis (8.3% vs. 2.6%, p = 0.001). Among the Ph-positive ALL cases, a high leukocyte count (n=151) was associated with a higher prevalence of pre-HSCT minimal residual disease (MRD) &amp;gt; 0.1% (n=88), which exhibited a significantly increased incidence of CNS relapse (16.6% vs. 6.8%, p = 0.009). Factors such as age, number of intrathecal chemotherapy treatments, conditioning intensity, and dose of anti-thymocyte globulin did not have a significant impact. Among the 34 patients with CNS relapse, 21 (61.7%) had isolated CNS relapse, and 7 of them showed evidence of positive MRD. With the exception of one patient who refused further treatment, the remaining 33 patients received initial CNS local therapy, including intrathecal chemotherapy combined with radiotherapy in 27 (82.0%) cases, intrathecal chemotherapy alone in 6 cases, and radiotherapy alone in 4 cases. Out of these patients, 22 were treated with dasatinib or ponatinib, while 6 received salvage chemotherapy. The median overall survival for patients with CNS relapse was 11.2 months, which was 19.8 months for those with isolated CNS relapse and 10.9 months for those with CNS relapse accompanied by bone marrow relapse (p = 0.077). The subsequent 2-year cumulative incidence of CNS relapse was 30%. Conclusion Based on our findings, the current prophylaxis strategy employed for the prevention of post-HSCT CNS relapse in adult ALL appears to be effective. However, our data indicates that MRD-positive Ph-positive ALL requires distinct management due to its significantly elevated risk of CNS relapse. New strategies including prophylactic radiotherapy for this high-risk subgroup must be considered to prevent post-HSCT CNS disease.

Incidence of Central Nervous System Relapse in Patients with Primary Mediastinal Large B-Cell Lymphoma: A Retrospective Study

Background Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon type of non-Hodgkin lymphoma. Clinicopathologic features are distinct from diffuse large B cell lymphoma, but it shares some clinical and biologic features with Nodular sclerosis classic Hodgkin lymphoma. Central nervous system (CNS) relapse appears to be rare in patients with PMBCL, with limited literature reporting a rate of approximately 1.5% to 4%. We examined the incidence of CNS relapse, treatment approaches and survival outcomes in patients with PMBCL. Methods Patients with newly diagnosed PMBCL seen at Mayo Clinic between 2002 and 2022 were identified using the prospective Mayo Clinic Lymphoma Database. Clinical features, treatment details and outcomes were abstracted from the medical record. Cumulative incidence of CNS relapse was analyzed with death as a competing risk. The association of CNS-IPI, systemic treatment, and CNS prophylaxis approach with CNS relapse rate was analyzed using competing risk models and descriptively. Event-free survival (EFS) for the cohort was defined as time from PMBCL diagnosis to first recorded CNS and/or systemic relapse or death from any cause. Overall survival (OS) was defined as time from PMBCL diagnosis (or CNS relapse) to death from any cause. Survival analysis was performed using the Kaplan-Meier method. Results A total of 124 PMBCL cases were identified. The median age at diagnosis was 37 years and 61% were female. The distribution of CNS-IPI was low-risk in 67 (61%), intermediate-risk in 41 (37%), and high-risk in 2 (2%). 64 patients (52%) received R-CHOP and 54 patients (44%) received R-DA-EPOCH as frontline therapy. High-dose methotrexate (HD-MTX) for CNS prophylaxis was administered to 6 patients (5%), 5 with R-CHOP and 1 with R-DA-EPOCH. 16 patients received intrathecal (IT) chemotherapy (methotrexate and/or cytarabine) for CNS prophylaxis, 3 with R-CHOP and 13 with R-DA-EPOCH. The median follow-up was 56.0 months. The 5-year EFS rate was 75.1% and the 5-year OS rate was 90.7% for the entire cohort. 20 patients had systemic relapse only and 3 had CNS relapse. The cumulative incidence of CNS relapse was 1.84% (95% CI 0.46%-7.17%) at 2 years and 2.92% (95% CI 0.50%-8.84%) at 5 years (Figure 1). No statistically significant association of CNS-IPI, systemic therapy or CNS prophylaxis regimen with CNS relapse rate was found in competing risk models; however, this analysis was limited by a small event number (n=3). Among the 3 patients with CNS relapse, 1 had high-risk CNS-IPI and 2 had intermediate risk. All 3 patients were treated initially with R-CHOP. Two patients did not receive any CNS prophylaxis and 1 patient received IT CNS prophylaxis. All three patients who had CNS relapse were female. Patient #1 was diagnosed at age 48 and had simultaneous CNS and systemic relapse 6 months later. The patient was treated with HD-MTX, temozolomide and rituximab for CNS relapse, and subsequently received multiple therapies for systemic disease including R-DHAP, R-ICE, and died 17 months after CNS relapse. Patient #2 was diagnosed at age 22 and had CNS relapse after 8.7 months, followed by systemic relapse 2 months later. The patient received HD-MTX, temozolomide and rituximab for CNS relapse, followed by systemic and whole-brain radiation therapy (RT) for both systemic and CNS relapse. Subsequently the patient received salvage chemotherapy, autologous and allogeneic stem cell transplant for systemic relapse. The patient died 26.8 months after CNS relapse. Patient #3 was diagnosed at age 24 and had systemic relapse after 20.7 months, followed by CNS relapse 5.4 months later. The patient received methotrexate and whole-brain RT following CNS relapse and died 1.2 months after CNS relapse. Besides these 3 patients, we identified 6 PMBCL patients with CNS relapse who were diagnosed at other medical centers and subsequently referred to our institution for management of refractory disease. The survival after CNS relapse was poor, with a median OS of 10.4 months (95% CI 5.6-15.2). Conclusion Our study showed that the CNS relapse rate (1.84% at 2 years and 2.92% at 5 years) was overall low in patients with PMBCL, consistent with previous reports. CNS relapse was associated with poor survival despite aggressive treatment approaches. Novel approaches utilizing biological risk factors for CNS relapse, such as circulating tumor DNA, are needed to identify patients with CNS relapse.

Picalm::MLLT10 can Identify a New Subgroup of Acute Leukemias of Ambiguous Lineage with Unique Extramedullary Disease and Treatment Response

Background: Mixed-phenotype acute leukemias (MPAL), which is included in acute leukemias of ambiguous lineage (ALAL), can be classified as four different subtypes based on recurring genetic alterations including BCR::ABL, KMT2A and ZNF384 gene rearrangement as well as BCL11B activation. The 2022 WHO classification has already mentioned PICALM::MLLT10 fusions are also enriched in MPAL but need more data. In 2022 ELN classification, PICALM::MLLT10 was identified as acute myeloid leukemia (AML) with other rare recurring translocations but not ALAL. In addition, there is no separate classification for PICALM::MLLT10 in the new ICC classification. Therefore, it is still confused whether PICALM::MLLT10 corresponds to AML or acute lymphoblastic leukemia (ALL) or ALAL. Methods: Fourteen PICALM::MLLT10 positive patients of 390 AL patients (14/390, 3.6%) were identified by RNA sequencing (RNA-seq) in our center from 2020-2022, including 8 female and 6 male, with a median age of 33 years (16-50 years). These patients were newly diagnosed AL according to bone marrow morphology and immunology including 5 ALAL, 5 T-ALL [ 4 early T-cell precursor ALL (ETP-ALL), 1 cortical T-ALL], 2 AML, 1 B-ALL with aberrant expression of myeloid antigen, and 1 B/T MPAL. Results: The mean white blood cell counts of these patients was 8.25×10 9/L (2.34-51×10 9/L) and platelet counts was 168.5×10 12/L (39-429×10 12/L) individually. It should be mentioned that extramedullary disease (EMD) was found in 7 cases (7/14), including mediastinum, tonsil, and skin. In terms of immunotyping, CD7 was identified in all patients (14/14) and CD33 in 71.4% (10/14) patients. The major concurrence mutations were PHF6 mutation (8/14), JAK3 mutation (5/14), and SUZ12 mutation (4/14). Characteristic cytogenetic abnormality t(10;11)(p12.3;q14.2) was only found in three cases (3/14) (Table 1). The PICALM breakpoints are mainly concentrated in exon 17 (n=6) and exon 19 (n=8). Exon 4 (n=8), exon 6 (n=2), exon 9 (n=2) and exon 10 (n=2) are the most commonbreakpointsof MLLT10. To our knowledge, this is the first report about the breakpoints and fusion gene forms of PICALM::MLLT10. For initial treatment, these patients individually received standard ALL induction chemotherapy (VDPCP, vincristine, idarubicin, pegaspargase, cyclophosphamide, prednisone) and AML induction chemotherapy (3+7 IA regimen including idarubicin, cytarabine). The initial complete remission (CR) rate was only 35.7% (5/14), and 9 patients showing no remission (NR). These NR patients subsequently received salvage chemotherapy. It is worth mentioning that 6 of them received combined chemotherapy regimen including low doses of cytarabine (LDAC), granulocyte colony-stimulating factor (G-CSF) and anthracyclines such as aclarubicin or idarubicin or homoharringtonine (CAG or IAG or HAG), and 2 of 6 patients also further received combination therapy with venetoclax (CAG or IAG +VEN). Finally, 5 of them dramatically achieved CR (5/6). In the other 3 patients, 1 patient who was failure to initial Hyper-CVAD A/B regimen also dramatically achieved CR after the more Hyper-CVAD A regimen combined with venetoclax, and 1 patient achieved CR while another still NR with both receiving CLAG (cladribine, cytarabine, G-CSF) regimen. Subsequently 11 patients (9 CR, 2 with refractory disease) received allogenic hematopoietic stem cell transplantation (allo-HSCT), and all the CR patients survived well after HSCT (follow up 3-24 months, median 15 months) without relapse, while 2 NR patients died soon after transplantation because of severe complications (Table 2). Conclusions: Our data suggested PICALM::MLLT10 positive AL should be more appropriately recognized as an independent ALAL entity and may benefit from LDAC, G-CSF and anthracyclines combination chemotherapy as well as venetoclax. Sequential HSCT after chemotherapy combined with venetoclax may further improve long-term survival in AL patients with CR even MRD positive.

Baseline circulating tumour DNA and interim PET predict response in relapsed/refractory classical Hodgkin lymphoma.

Reliable biomarkers for early identification of treatment failure in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) are lacking. Circulating tumour DNA (ctDNA) profiling has emerged as a powerful predictive and prognostic tool in several haemopoietic and non-haemopoietic malignancies and may guide rational treatment choices in r/r cHL. To assess the predictive and prognostic value of ctDNA, we performed a retrospective analysis on 55 r/r cHL patients treated with the bendamustine, gemcitabine and vinorelbine (BEGEV) regimen and additionally evaluated the potential utility of integrating ctDNA with interim [18 F]-FDG positron emission tomography (iPET). Baseline ctDNA genotyping in r/r cHL mirrored gene mutations and pathways involved in newly diagnosed cHL. We found that baseline ctDNA quantification and serial ctDNA monitoring have prognostic value in r/r cHL receiving salvage chemotherapy. Lastly, integrating ctDNA quantification with iPET evaluation may improve the early identification of patients at high risk of failing standard salvage therapy, who may benefit from an early switch to immunotherapeutic agents. Collectively, our results support the implementation of non-invasive methods to detect minimal residual disease in recurrent cHL and justify its prospective evaluation in appropriately designed clinical trials.

Treatment of Recurrent Orbital Rhabdomyosarcoma with Exenteration and HDR Brachytherapy in a Custom Mold

Rhabdomyosarcoma (RMS) is the most frequent cancer affecting the orbit in children. The orbit is classified as a favorable site for RMS as treatment with chemotherapy and radiation is effective. Local failure for patients with RMS of the orbit has ranged from 2-16% on IRS and COG protocols. In the event of local recurrence, survival is poor, and management is difficult. We report four patients with local recurrence of orbital RMS managed with orbital exenteration followed by high dose rate (HDR) brachytherapy. Four patients were treated from 2016-2022. HDR brachytherapy with Ir-192 was delivered in a custom mold of the orbit made after the orbital exenteration procedure. Brachytherapy was given in 6-7 twice daily (BID) fractions starting 1 week after the orbital exenteration. At the time of brachytherapy, patient ages were 3, 1, 7, and 7 years. Three patients had embryonal histology and underwent initial systemic therapy with ARST0331 regimen A. The fourth patient had alveolar, FOXO1 fusion positive RMS and was initially treated as per COG D9803 regimen A. All patients had received proton radiotherapy as part of initial treatment. Three received 50.40 Gy and one received 45 Gy. Patients developed biopsy-proven, recurrent disease an average of 56 weeks (range 38-77) after initial diagnosis. All patients received salvage chemotherapy before undergoing orbital exenteration at an average of 12 weeks after recurrence (range 5-16). Three patients received 30 Gy in 6 BID fractions, and one patient received 28 Gy in 7 fractions with HDR brachytherapy using an Ir-192 source. All four patients are alive without evidence of disease at an average of 27 months (range 6-70) from recurrence and 39 months (range 21-78) from initial diagnosis. All patients have acceptable orbit healing. Two patients have asymptomatic evidence of frontal lobe edema (and in one case possible necrosis) extending 1-2 cm above the orbit. This appears to be beyond the range of the brachytherapy dosimetry, but the combination of proton beam and brachytherapy are implicated. No other toxicities have occurred. Orbital RMS has a favorable prognosis, but local failure after initial combined modality therapy can be fatal. Options for successful local salvage are limited. Orbital exenteration with HDR brachytherapy in a custom mold is an effective and safe procedure for local control in these difficult cases.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers

PurposeTo evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. Methods and MaterialsSeventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. ResultsMedian age at recurrence was 55 years (Range: 35–73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30–50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. ConclusionThe use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

​Occult extracranial malignancy after complete remission of pineal mixed germ cell tumors: a rare case report and literature review

Background​Extracranial metastasis can occur in intracranial germ cell tumors (GCTs), but it is very rare. Recurrence or metastasis of non-germinomatous germ cell tumors (NGGCTs) is often accompanied by elevated tumor markers. ​Occult extracranial metastases or recurrences with negative markers are often difficult to detect in time, resulting in a very poor prognosis.Case presentationA 12-year-old boy was admitted to our institution with dizziness, headache, vomiting, and sleepiness. Magnetic resonance imaging (MRI) showed a pineal mass, accompanied by a significant increase in serum alpha-fetoprotein (AFP). The patient subsequently underwent total removal of the tumor. Pathology revealed that the tumor was a mixed GCT, consisting of mature teratoma, germinoma, and yolk sac tumor. Intracranial GCT achieved complete remission after intensive adjuvant chemotherapy and radiotherapy. Regular follow-up MRI revealed no recurrence of the intracranial tumor and continued monitoring of tumor markers revealed no abnormalities. ​Eight months later, the patient was readmitted due to progressive abdominal pain. Imaging and physical examination revealed abdominal occupation and lymphatic mass in the neck. He received salvage chemotherapy, anti-PD-1 immunotherapy, and palliative chemotherapy, but still developed multiple organ dysfunction syndromes (MODS) due to tumor progression and eventually died after one month.Conclusions​This profound case suggests that intracranial NGGCTs may develop occult extracranial malignancy, which can be very severe at the time of clinical symptoms and has an extremely poor prognosis. Therefore, in addition to tumor marker monitoring, regular follow-up with extracranial imaging may be warranted to detect extracranial tumors as early as possible, although perhaps not as frequently as with neuroimaging.

Glofitamab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Glofitamab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Treatment outcomes and prognostic factors in children with hepatoblastoma using a risk‐stratified approach

Not all the significant progress made in the management of children with hepatoblastoma (HB) has translated into improved outcomes in limited-resource settings. There are limited data on outcomes in children with HB from India. All patients diagnosed with HB between July 2013 and December 2020 were risk-stratified and treated as per International Liver Tumor Strategy Group (SIOPEL). Patients with standard-risk HB received cisplatin monotherapy and those with high-risk HB received alternating cycles of cisplatin and the combination of carboplatin plus doxorubicin. Data regarding demographic details, chemotherapy, surgery, liver transplantation, outcomes, prognostic factors, and toxicity were collected. Of 157 patients with HB, 117 (74%) were high risk, 31 (20%) were standard risk, and nine (6%) unknown. Patients with standard-risk disease had excellent outcomes, with 3-year event-free survival (EFS) and overall survival (OS) of 96% and 100%, respectively. Among high-risk HB, six underwent orthotopic liver transplantation of which four were alive at last follow-up. The 3-year EFS and OS of patients with high-risk disease was 56% and 66%, respectively. Outcomes of patients with PRETEXT IV (3-year EFS: 42%, 3-year OS: 50%) and metastatic disease (3-year EFS: 30%, 3-year OS: 50%) were dismal. Patients with serum alpha-fetoprotein (AFP) reduction greater than 90% following two courses of chemotherapy had favorable outcomes; 3-year EFS: 80% versus 58% (p=.013) and 3-year OS: 95% vs. 68% (p<.01). Only two (6%) of 31 patients with relapse/refractory HB were alive at a median follow-up of 36months, and both had received salvage chemotherapy and surgery. While children with standard-risk HB had excellent outcomes, those with high-risk disease continue to do poorly. Serial monitoring of serum AFP values is a cost-effective and reliable predictor of outcomes. Orthotopic liver transplantation remains a viable option for inoperable disease in resource-limited settings as well.

MP50-16 ONCOLOGICAL OUTCOMES FOLLOWING ROBOTIC POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR TESTICULAR CANCER: A WORLDWIDE MULTICENTER STUDY

You have accessJournal of UrologyCME1 Apr 2023MP50-16 ONCOLOGICAL OUTCOMES FOLLOWING ROBOTIC POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR TESTICULAR CANCER: A WORLDWIDE MULTICENTER STUDY Alireza Ghoreifi, Anirban Mitra, Ashish Khanna, Jordan Rich, George McClintock, Fady Baky, Zachary Mcdowell, Matthew Ho, Jacob Roberts, Farshad Sheybaee Moghaddam, Taseen Haque, Inderbir Gill, Scott Eggener, James Porter, Nariman Ahmadi, Reza Mehrazin, John Sfakianos, Aditya Bagrodia, Sudhir Rawal, John Ward, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi More articles by this author , Anirban MitraAnirban Mitra More articles by this author , Ashish KhannaAshish Khanna More articles by this author , Jordan RichJordan Rich More articles by this author , George McClintockGeorge McClintock More articles by this author , Fady BakyFady Baky More articles by this author , Zachary McdowellZachary Mcdowell More articles by this author , Matthew HoMatthew Ho More articles by this author , Jacob RobertsJacob Roberts More articles by this author , Farshad Sheybaee MoghaddamFarshad Sheybaee Moghaddam More articles by this author , Taseen HaqueTaseen Haque More articles by this author , Inderbir GillInderbir Gill More articles by this author , Scott EggenerScott Eggener More articles by this author , James PorterJames Porter More articles by this author , Nariman AhmadiNariman Ahmadi More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , John SfakianosJohn Sfakianos More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Sudhir RawalSudhir Rawal More articles by this author , John WardJohn Ward More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The feasibility and safety of robotic approach for post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) has been previously shown by our group. The aim of this study is to evaluate the oncological outcomes of robotic PC-RPLND. METHODS: In this retrospective study, we included patients who underwent robotic PC-RPLND at nine academic centers across the world between 2011 and 2022. Patients’ characteristics, pathological findings, and oncological outcomes were reviewed. RESULTS: A total of 137 patients with a median age of 29 (IQR 25, 36) years were included. The baseline features and clinicopathological findings are shown in Table 1. BEP (bleomycin, etoposide, cisplatin) was the main chemotherapy regimen (80%) and 12 patients (9%) received salvage chemotherapy. Twelve cases (9%) were electively converted to open. Median estimated blood loss, operative time, and length of hospital stay were 100 mL, 5 hours, and 2 days, respectively. Final pathology revealed necrosis/fibrosis in 59 (43%), pure teratoma in 64 (47%), and viable germ cell tumor in 14 (10%) patients. Among patients with residual viable tumor, those with pN2,3 non-seminoma received chemotherapy and the others were followed closely. With a median follow-up of 21 (IQR 8, 49) months, seven patients (5%) had disease recurrence, of whom 3 (2%) were in-field (Table 2). 2-year recurrence free survival was 93%. Median time to recurrence was 11 months. No port-site recurrence or carcinomatosis was identified. Two (1.5%) cancer-related deaths were recorded. CONCLUSIONS: At centers with expertise in testicular cancer and minimally invasive surgery, in appropriately selected patients robotic PC-RPLND is associated with comparable short-term oncological outcomes to the open approach. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e691 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Anirban Mitra More articles by this author Ashish Khanna More articles by this author Jordan Rich More articles by this author George McClintock More articles by this author Fady Baky More articles by this author Zachary Mcdowell More articles by this author Matthew Ho More articles by this author Jacob Roberts More articles by this author Farshad Sheybaee Moghaddam More articles by this author Taseen Haque More articles by this author Inderbir Gill More articles by this author Scott Eggener More articles by this author James Porter More articles by this author Nariman Ahmadi More articles by this author Reza Mehrazin More articles by this author John Sfakianos More articles by this author Aditya Bagrodia More articles by this author Sudhir Rawal More articles by this author John Ward More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF downloadLoading ...

MP50-08 POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR SEMINOMA: IS SURGERY EFFECTIVE?

You have accessJournal of UrologyCME1 Apr 2023MP50-08 POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR SEMINOMA: IS SURGERY EFFECTIVE? Isamu Tachibana, Andre Alabd, Rumeal Whaley, Jacob Mcfadden, Alex Piroozi, Sean Kern, Nabil Adra, Richard Foster, Lawrence Einhorn, Clint Cary, and Timothy Masterson Isamu TachibanaIsamu Tachibana More articles by this author , Andre AlabdAndre Alabd More articles by this author , Rumeal WhaleyRumeal Whaley More articles by this author , Jacob McfaddenJacob Mcfadden More articles by this author , Alex PirooziAlex Piroozi More articles by this author , Sean KernSean Kern More articles by this author , Nabil AdraNabil Adra More articles by this author , Richard FosterRichard Foster More articles by this author , Lawrence EinhornLawrence Einhorn More articles by this author , Clint CaryClint Cary More articles by this author , and Timothy MastersonTimothy Masterson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with relapsed seminoma after first-line chemotherapy can be treated with salvage chemotherapy or post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND). Based on prior reported experience, surgical management can have worse efficacy and increased morbidity compared to non-seminomatous germ cell tumor. Our aim was to characterize the surgical efficacy and difficulty in a specific cohort of patients with definite progression but minimal disease burden. METHODS: The Indiana University testis cancer database was queried to identify men who underwent PC-RPLND for seminoma between January 2011 to December 2021. Included patients only underwent first-line chemotherapy and could not have any evidence of non-seminomatous elements on orchiectomy or have elevated serum alpha-fetoprotein (AFP). All patient demonstrated high suspicion of retroperitoneal disease prior to PC-RPLND was based on increasing size of tumor on standard CT imaging, progression of FDG avidity on PET imaging, or elevated tumor markers. RESULTS: We identified 889 patients that underwent PC-RPLND, of which only 14 patients were operated on for seminoma. One patient was excluded for lack of meaningful follow-up. Out of 13 patients, only 3 patients were disease free with surgery and did not have to undergo salvage chemotherapy. Median follow up time was 29.9 months (IQR: 22.6-53.7). Two patients died due to testicular cancer. The remaining 8 patients were treated successfully with salvage chemotherapy. For additional procedures, 4 patients required a nephrectomy, 1 patient required an aortic graft, 2 patients required a partial ureterectomy, and 3 patients required partial or complete caval resection CONCLUSIONS: The decision between salvage chemotherapy and PC-RPLND as second-line therapy can be challenging. Salvage chemotherapy is effective but is associated with short and long-term morbidity. Surgical efficacy in this setting seems to be limited, but careful selection of patients may lead to surgical success without life threatening morbidity or adjunctive procedures that may compromise the ability to receive salvage chemotherapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e687 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Isamu Tachibana More articles by this author Andre Alabd More articles by this author Rumeal Whaley More articles by this author Jacob Mcfadden More articles by this author Alex Piroozi More articles by this author Sean Kern More articles by this author Nabil Adra More articles by this author Richard Foster More articles by this author Lawrence Einhorn More articles by this author Clint Cary More articles by this author Timothy Masterson More articles by this author Expand All Advertisement PDF downloadLoading ...

Peritransplant Radiation Therapy in Patients With Refractory or Relapsed Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant: Long-Term Results of a Retrospective Study of the Fondazione Italiana Linfomi

In this multicenter collaboration, we report real-world data in the largest published series of long-term outcomes for patients with relapsed/refractory (r/r) Hodgkin lymphoma (HL) treated with peritransplant radiation therapy (pt-RT) and high-dose chemotherapy with autologous stem cell transplant (ASCT). We conducted a retrospective analysis including data from 12 institutions. Eligibility required histologic diagnosis of HL, receipt of ASCT plus pt-RT between 2004 and 2014 for r/r HL, and age ≥18 years at the time of ASCT. All patients received salvage chemotherapy for maximum debulking before ASCT. Metabolic responses were scored according to the Lugano Classification. The primary endpoint was overall survival (OS). Univariate and multivariate Cox proportional hazards were calculated to estimate the effect of covariates on patients' outcome. One hundred thirty-one patients were eligible: 68 were male (52%), and median age at ASCT was 32 years (range, 18-70). At the time of diagnosis with r/r HL, 92 patients (70%) had limited (stage I-II) disease, and 10 patients (8%) had bulky disease. Pt-RT was given pre-ASCT in 32 patients (24%) and post-ASCT in 99 (76%); median prescribed dose was 30.6 Gy (range, 20-44 Gy). With median follow-up of 60 months, 3- and 5-year OS were 84% and 77%, while 3- and 5-year progression-free survival were 75% and 72%, respectively. On univariate and multivariate analysis, advanced stage at relapse (hazard ratio [HR], 2.18; P=.04), irradiation of >3 sites (HR, 3.69; P=.01), and incomplete metabolic response after salvage chemotherapy (HR, 2.24; P=.01) had a negative effect on OS. The sequencing of pt-RT (pre- vs post-ASCT) did not affect outcomes. Overall, the addition of pt-RT to ASCT for patients with r/r HL is associated with very good outcomes. Limited relapsed disease with ≤3 sites involved and achievement of complete metabolic response after salvage chemotherapy were predictive of more favorable prognosis.

Oncologic outcomes following post-cystectomy recurrence of bladder cancer based on metastatic site and role of salvage immunotherapy.

574 Background: To evaluate how the location of bladder cancer recurrence after radical cystectomy (RC) affects survival and assess the role of salvage immunotherapy in this setting. Methods: On retrospective review of 4093 patients from our institutional IRB approved cystectomy database from January 1971 to December 2021, we identified 889 patients who underwent RC with curative intent and have been detected with recurrence of bladder cancer. Patients with urethral and ureteral recurrence were excluded. The data was then stratified based on the site of recurrence. Results: In this cohort of 889 patients (median age of 68, 77% male), the most common sites of metastases were widespread (48%), local (15%), lung (10%), bone (8%), retroperitoneal nodes (5.5%), liver (5%) and brain (1.5%) in order. With a median of 8.4 months, bone metastasis had shortest length from cystectomy to recurrence, while liver metastasis had shortest post recurrence survival (median of 4 months). For distant recurrence alone, only 33% survived past the first year. Salvage immunotherapy was administered in 8% of the patients and 47% received salvage chemotherapy. On multivariate analysis, liver metastasis (HR 2, 95%CI 1.4-2.9), widespread metastasis (HR 1.9, 95%CI 1.5-2.4), pathological staging&gt;T3 (HR 1.3, 95%CI 1.1-1.6) and nodal involvement at the time of RC (HR 1.5, 95%CI 1.2-1.7) were significantly associated with worse survival after the recurrence. Salvage immunotherapy provided a significant improvement in post-recurrence survival (HR 0.2, 95% CI 0.1-0.3). Conclusions: Liver, brain, and widespread metastases predominantly showed the lowest chance of survival past one year from recurrence; however, more than half of all patients with recurrence did not live past the first year. Salvage immunotherapy may lead to a better prognosis in recurrence post-cystectomy. [Table: see text]