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Emergent genomic analytic techniques in patients with cancer offer the potential to define the risk of myelo dysplastic syndrome (MDS) and acute leukemia (AL) manifesting following targeted radionuclide therapy of metastatic lymphoma, neuroendocrine tumors (NETs), and prostate cancer. Characterization of the genetic profile will allow risk stratification of patients before theranostic radionuclide management of advanced cancers and offers the opportunity to minimize toxicity while preserving optimal individualized efficacy in the practice of personalized precision nuclear oncology. Our review of a single-center experience of prospective radionuclide theranostic management of metastatic non-Hodgkin lymphoma (NHL), NETs, and castration-resistant prostate cancer (metastatic castrate-resistant prostate cancer [mCRPC]) over the past decade, and comparison with published studies, shows that while the risk of significant myelotoxicity is generally low, at <3%, the consequences in the small minority of patients who develop MDS or AL are substantial, and survival is poor. Timely identification of patients at heightened risk of hematologic toxic complication, using novel genomic technology before institution of radionuclide therapy, will facilitate amelioration of myelotoxicity. In current clinical practice, the minimal hematological toxicity of chemo-free theranostic management of advanced cancer is significantly less compared with newly adopted chemotherapy -immunotherapy regimens, and the financial toxicity associated with these novel agents is avoided. [ABSTRACT FROM AUTHOR]

First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. Keywords: radioimmunotherapy; MDS; acute leukaemia; follicular lymphoma; haemotoxicity EN radioimmunotherapy MDS acute leukaemia follicular lymphoma haemotoxicity 237 241 5 12/27/21 20220101 NES 220101 Advances in the treatment of follicular lymphoma (FL) have fostered the hope that some patients may be cured with the use of immunochemotherapy. Fractionated 90Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: nine-year updated results from the StiL NHL1 study. [Extracted from the article]

Thirty-seven patients with advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) were treated on a prospective phase II single-center study with four cycles of 7.8 GBq 177Lu-octreotate combined with capecitabine and temozolomide chemotherapy (CAPTEM). Each 8-week cycle combined radiopeptide therapy with 14 days of capecitabine (1500 mg/m2) and 5 days of temozolomide (200 mg/m2). The incidence of grade ≥ 3 hematologic toxicity was analyzed. At a median follow-up of 7-years (range 1-10), six (16%) patients developed persistent hematologic toxicity (PHT) (defined as sustained grade ≥ 3 hematologic toxicity beyond 36-months follow-up) and three (8%) developed MDS/AL with a median time-to-event of 46 and 34 months, respect ively. The estimated cumulative incidence of MDS/AL was 11% (95% CI: 3.45-24.01). Development of PHT was the only significant risk factor for secondary MDS/AL (RR, 16; 9 5% CI: 2.53 to 99.55; P < 0.001). The median PFS was 48 months (95% CI: 40.80-55.20), and the median OS was 86 months (95% CI: 56.90-115.13). Twenty-one deaths were recorded, including 13 (62%) due to progressive disease and all 3 (14%) patients with MDS/AL. 177Lu-octreotate CAPTEM therapy for GEPNETs is associated with a risk of long-term hema tologic toxicity. The rising cumulative incidence of MDS/AL > 10% mandates the long-term monitoring of treated patients. However, time to onset is unpredictable, and incidence does not correlate with conventional baseline risk factors. Novel methods are required for the stratification of prospective patients based on genetic risk. [ABSTRACT FROM AUTHOR]

Background: The combination of radiopeptide therapy [peptide receptor radionuclide therapy (PRRT)] with radiosensitizing chemotherapy of gastroenteropancreatic neuroendocrine tumors (GEP NETs) may improve efficacy, but has the potential to increase myelotoxicity. In a prospective clinical study of GEP NET patients treated with 177Lu-octreotate PRRT in combination with capecitabine and temozolomide, as a prelude to a planned Australasian Gastro-Intestinal Trials Group (AGITG) international randomized controlled trial, we characterized the incidence and degree of hematological toxicity. Materials and Methods: Well-differentiated progressive metastatic GEP NETs in 65 patients were treated with 4 cycles of 7.8 GBq 177Lu-octreotate, 1,650 mg/m2 capecitabine (n = 28) and 1,500 mg/m2 capecitabine with 200 mg/m2 temozolomide (n = 37), and monitored for hematological toxicity over a 5-year period. Results: Short-term, self-limited hematological toxicity grade 3/4 comprised anemia in 1 patient (3.5%) in the 28 patient-cohort of patients treated with 177Lu-octreotate and capecitabine. One of these patients (3.5%) later developed significant anemia and one developed thrombocytopenia (3.5%) over a median follow-up of 60 months (SD 20). The incidence of short-term grade 3/4 reversible myelosuppression in 37 patients after 177Lu-octreotate/capecitabine/temozolomide was zero. Long- term follow-up for a median of 36 months (SD 11) showed significant thrombocytopenia in 2.7% and neutropenia in 2.7% of the patients and anemia in 10.8% of the patients (n = 4). The 3-year median hemoglobin and platelet and neutrophil counts trended downwards, but remained within normal ranges. Two patients in this cohort developed myelodysplastic syndrome. Conclusion: The modest reversible hematological toxicity of PRRT of GEP NETs is not significantly increased by the addition of radiosensitizing chemotherapy with capecitabine and temozolomide in combination with 177Lu-octreotate, which has the potential to enhance the efficacy of radiopeptide therapy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]