Consolidation Chemotherapy

BackgroundTreatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL.Methods/designThis multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment.DiscussionThe studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance, adverse events and surgical complications. We will measure QoL in both groups. We will analyze molecular indications that may lead to more individually tailored treatments in the future. This will be the first NOM trial utilizing a regression schema for response assessment in a prospective fashion.Trial registrationNCT02008656.

BackgroundPersons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple consolidation chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction chemotherapy and DLI.MethodsForty-seven subjects with acute leukemia relapsing after an allotransplant and who achieved complete remission after post-relapse induction chemotherapy and DLI were eligible. The use of consolidation chemotherapy and DLI was guided by the results of MRD testing and whether or not DLI caused acute and/or chronic GvHD. Outcomes were compared with those of 34 similar historical controls who did not receive consolidation chemotherapy and DLIs after induction chemotherapy and DLI.ResultsOne-year cumulative incidence of relapse (CIR; 22 % 95 % confidence interval (10, 35 %) vs. 56 % (39, 73 %); P ConclusionThese data suggest MRD- and GvHD-guided multiple consolidation chemotherapy and DLIs reduce CIR and increase LFS and survival compared with controls in persons relapsing after allotransplant for acute leukemia.Trial registrationChiCTR-ONC-12002912 . Donor lymphocyte infusion for the treatment of leukemia relapse following allogeneic hematopoeitic stem cell transplant.

BackgroundNeoadjuvant CRT may lead to significant tumor regression in patients with rectal cancer. Different CRT regimens with consolidation chemotherapy may lead to increased rates of complete tumor regression. The purpose of this study was to understand tumor metabolic activity following two different neoadjuvant CRT regimens using sequential PET/CT imaging in two different intervals following RT.MethodsPatients with cT2-4 N0-2 M0 rectal cancer treated by standard CRT (54Gy and 2 cycles of 5FU-based chemotherapy) or extended CRT (54Gy and 6 cycles of 5FU-based chemotherapy) underwent sequential PET/CT imaging at baseline, 6 weeks and 12 weeks from radiation completion.Results99 patients undergoing standard CRT were compared to 12 patients undergoing CRT with consolidation chemotherapy. Patients treated with consolidation CRT had increased rates of complete clinical or pathological response (66 % vs. 23 %; p ConclusionsMost of the reduction in tumor metabolism after neoadjuvant CRT occurs within the first 6 weeks from RT completion. In patients undergoing CRT with consolidation chemotherapy, tumors are less likely to regain metabolic activity between 6 and 12 weeks. Therefore, assessment of tumor response may be safely postponed to 12 weeks in patients undergoing extended CRT with consolidation chemotherapy.Trial registrationNCT00254683.

Secondary central nervous system lymphoma (SCNSL) remains a rare but challenging manifestation of aggressive lymphomas, with limited prospective data to guide treatment decisions in the modern therapeutic era. We conducted a multicentre retrospective cohort study of 105 consecutively treated adult patients diagnosed with SCNSL between 2016 and 2024 across four German academic centres, capturing detailed treatment sequencing, response dynamics and outcome data. Median progression-free survival (PFS) was 7.62 months (95% CI 5.34-9.90), and median overall survival (OS) was 16.62 months (95% CI 5.91-27.33). Consolidation with high-dose chemotherapy and autologous haematopoietic stem cell transplantation (HDT-AHSCT) was associated with significantly improved OS and PFS in univariate and multivariate analyses. Achieving complete remission prior to HDT-AHSCT conferred with superior outcomes. In a small subset of patients with relapsed/refractory (rr) SCNSL, CD19-directed chimeric antigen receptor T-cell (CAR T) therapy showed favourable outcomes compared with non-transplant salvage therapy in exploratory univariate analysis (OS HR 0.28, 95% CI 0.08-0.94, p = 0.039; PFS HR 0.37, 95% CI 0.16-0.88, p = 0.025). In this contemporary multicentre real-world cohort, early response and consolidative HDT-AHSCT emerged as key determinants of durable disease control, while CAR T therapy may represent a salvage strategy for selected patients. These findings provide clinically relevant benchmarks to inform risk-adapted treatment sequencing in SCNSL.