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Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45-2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin's lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events., Purpose: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL., Methods: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups., Results: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment., Conclusion: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Bleomycin is an antibiotic with cytotoxic properties that is commonly used in combination regimens for the treatment of Hodgkin lymphoma. The inconsistency in the dosage nomenclature of bleomycin appears universally, which increases the risk of medication errors. However, to the best of our knowledge, no such cases have been reported. Herein, we present a rare case report of a medication error caused by a bleomycin overdose. At the third cycle of chemotherapy, a 25-year-old patient with stage II Hodgkin lymphoma received a 10 times higher dose of bleomycin (150 USP) than that usually used as part of the doxorubicin, bleomycin, vindesine and dacarbazine protocol (ABVD). After the medication error was discovered, the patient was immediately treated with intravenous rehydration and furosemide to promote drug clearance. Additionally, methylprednisone and acetylcysteine were administered to prevent lung injury. However, the patient developed slight nausea and mild rash, which gradually improved after treatment. After evaluation with positron emission spectrometry-computed tomography (PET-CT), the patient received four cycles of AVD chemotherapy. No other obvious abnormalities were observed during the treatment and 1-year follow-up period. Hence, the toxicities, clinical management and selection of further chemotherapy after bleomycin overdose in such cases deserved serious attention. More importantly, management measures after this error may be used as a reference in other hospitals., (© 2023 British Pharmacological Society.)

Background: Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles., Methods: This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m 2 intravenously on days 1-3), doxorubicin (35 mg/m 2 intravenously on day 1), and cyclophosphamide (1250 mg/m 2 intravenously on day 1), and standard doses of bleomycin (10 mg/m 2 intravenously on day 8), vincristine (1·4 mg/m 2 intravenously on day 8), procarbazine (100 mg/m 2 orally on days 1-7), and prednisone (40 mg/m 2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503)., Findings: Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24-42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65-0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45-0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6-96·1) for BrECADD and 90·9% (88·7-93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7-99·5) and 98·2% (97·2-99·3), respectively., Interpretation: BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma., Funding: Takeda Oncology., Competing Interests: Declaration of interests PB reports consulting fees from Takeda, BMS, Roche, Amgen, Novartis, Celgene, Miltenyi Biotech, and Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, Novartis, BMS, Roche, MSD, Celgene, Miltenyi Biotech, Gilead, and AbbVie; and funding for scientific research from Takeda Oncology, MSD, and Novartis. JF reports funding and consulting fees from Takeda Oncology and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda Oncology and Roche Pharma. RG reports consulting fees from Celgene, Novartis, Roche, Takeda, AbbVie, Astra Zeneca, MSD, Merck, Gilead, Daiichi Sanko, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, and Sanofi; support for attending meetings or travel from Roche, Amgen, Janssen, Astra Zeneca, Novartis, BMS, AbbVie, and Daiichi Sankyo; participating on a data safety monitoring board or advisory board for Celgene, Novartis, Roche, BMS, Takeda, AbbVie, Astra Zeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, and Sanofi; and stock or stock options from Novo Nordisk and Lilly. MHe reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda. AH reports payment for speakers bureau, funding, and travel support from, and participation on an advisory board for Takeda. FK reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, and support for attending meetings or travel from Takeda. MHä reports consulting fees from Pfizer, Incyte, Roche, Amgen, Sanofi/Aventis, Sobi, Kite/Gilead, Janssen, and BMS and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sobi, Novartis, Kite/Gilead, Falk Foundation, and BMS. UN reports consulting fees for the institution from Janssen-Cilag, Celgene (BMS), Takeda, AstraZeneca, Roche, Novartis, Incyte, BeiGene, Kyowa Kiin, Gileag, and Pierre Fabre; payment or honoraria for lectures, presentations, speakers bureaus, manuscript, writing or educational events for the institution from Celgene (BMS), Novartis, Takeda, and Gilead; support to the institution for attending meetings or travel from Janssen, Roche, Gilead, and Takeda; and participating on a data safety monitoring board or advisory board for Janssen-Cilag, Celgene (BMS), Takeda, AstraZeneca, Roche, Novartis, Incyte, BeiGene, Kyowa Kiin, Gileag, and Pierre Fabre. JM reports consulting fees from MSD. AZi reports payment for presentations from Novartis, Oncopeptides, Takeda, Incyte, and Roche and travel support from Oncopeptides, Roche, and Novartis. AF reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda. AV reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, BMS, and AbbVie; support for attending meetings or travel from Janssen, Kite/Gilead, BMS, and AbbVie; and participation on a data safety monitoring board or advisory board from Roche, BMS, AbbVie, and Kite/Gilead. SS reports travelling support from AbbVie and Jazz and reports support for attending meetings or travel from and having a leadership or fiduciary role in another board, society, committee or advocacy group (paid or unpaid) with Pfizer, Amgen, and Novartis. VV reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda and participation on an advisory board for Takeda and MSD. AK reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Celgene, AbbVie, Sobi, BMS, and Takeda and support for attending meetings or travel from AbbVie, BeiGene, Sobi, Takeda, EUSA Pharma, Novartis, and Alexion. KT-G reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda. PK reports travel support from Roche Pharmaceuticals and Takeda. BvT reports institutional grants or contracts from Esteve, Merck Sharp & Dohme, Novartis, and Takeda; consulting fees from Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Roche, Sobi, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Lilly, Merck Sharp & Dohme, Novartis, Roche, and Takeda; support for attending meetings or travel from AbbVie, AstraZeneca, Gilead, Kite, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis; payment from Takeda and Regeneron (INSIGHTFUL study); payment to institution from the Olympia 3 study; and participation on a data safety monitoring board or advisory board for Takeda and Regeneron. SB reports consulting fees from Galapagos; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and consultation from Takeda; support for attending meetings or travel from Takeda; having a leadership role in another board, society, committee, or advocacy group (paid or unpaid), and holding stock or stock options for Liqomics. KB reports funding and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda Oncology. MF reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Celgene, BMS, Takeda, and Janssen. AZo reports Takeda stocks and being an employee of Takeda Oncology. SK reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, payment for expert testimony, and support for attending meetings or travel from, and participating on a data safety monitoring board or advisory board for Takeda. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This multicenter, single-arm, open-label, phase Ib study was designed to determine the recommended phase II dose (RP2D) and to evaluate the safety and preliminary efficacy of unesbulin plus dacarbazine (DTIC) in patients with advanced leiomyosarcoma (LMS)., Patients and Methods: Adult subjects with locally advanced, unresectable or metastatic, relapsed or refractory LMS were treated with escalating doses of unesbulin orally twice per week in combination with DTIC 1,000 mg/m 2 intravenously (IV) once every 21 days. The time-to-event continual reassessment method was used to determine the RP2D on the basis of dose-limiting toxicities (DLTs) assessed during the first two 21-day treatment cycles. All explored doses of unesbulin (200 mg up to 400 mg) were in combination with DTIC. An expansion cohort was enrolled to evaluate the safety and efficacy of unesbulin at the RP2D., Results: Unesbulin 300 mg administered orally twice per week in combination with DTIC 1,000 mg/m 2 IV once every 21 days was identified as the RP2D. On the basis of data from 27 subjects who were deemed DLT-evaluable, toxicity was higher in the unesbulin 400 mg group, with three of four subjects (75%) experiencing DLTs versus one of four subjects (25%) in the 200 mg group and three of 19 subjects (15.8%) in the 300 mg group. The most commonly reported DLTs and treatment-related grade 3 and 4 adverse events were thrombocytopenia and neutropenia. At the RP2D, seven subjects who were efficacy evaluable achieved partial response for an objective response rate of 24.1%., Conclusion: Unesbulin 300 mg twice per week plus DTIC 1,000 mg/m 2 once every 21 days was identified as the RP2D, demonstrating a favorable benefit-risk profile in a heavily pretreated population of adults with advanced LMS.

Background/aim: There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population., Patients and Methods: We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized., Results: At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm 2 Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients., Conclusion: MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Combination checkpoint inhibitor (CPI) and chemotherapy is an effective and safe treatment strategy for patients with untreated classic Hodgkin lymphoma. Recent studies of programmed cell death protein 1 inhibitors combined with doxorubicin, vinblastine and dacarbazine have demonstrated high overall and complete response rates. This combination has a unique toxicity profile that should be managed appropriately so as not to compromise treatment efficacy. Common toxicities include rash, hepatoxicity, neutropenia and thyroid dysfunction. Here, we present four cases and the management strategies around such toxicities. In addition, we highlight key clinical decision-making around the administration of subsequent doses of CPI and chemotherapy., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Hodgkin lymphoma (HL) occuring during pregnancy is a rare condition, and management relies on sparse literature. The specificity of pregnancy requires the clinician to take into account the clinical emergency, the stage of the lymphoma, the trimester of pregnancy, and the patient's choices. The main objective is twofold: to limit the risk of toxicity and adverse events for both mother and fetus, without reducing the chances of a successful outcome. Current literature data suggest that the use of ABVD-type polychemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is associated with obstetrical events and long-term fetal toxicity. We report here the results of a homogeneous management considering wait-and-see, vinblastine monotherapy and ABVD polychemotherapy options. The outcomes in terms of obstetrical complications, response rate, and overall survival (100 %) reinforce the idea that strategies that do not involve the use of multidrug therapy are possible and are associated with very good results., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B)., Materials and Methods: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points., Results: One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80)., Conclusion: The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era.

Purpose: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data., Methods: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data., Results: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation., Conclusion: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)., Patients and Methods: Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models., Results: With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%)., Conclusions: Combining baseline TLG with IPS could improve PFS prediction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result., (© 2023. The Author(s).)

Purpose: Hodgkin's lymphoma is currently treated with a chemotherapy protocol consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine. Due to Brazil facing a bleomycin shortage in 2017, and this drug's high toxicity, this retrospective study evaluates the effect that the absence of bleomycin had on treatment response and overall survival of Hodgkin's lymphoma patients., Methods: The medical records of 126 HL patients treated between 2007 and 2021 were reviewed and their data collected, followed by grouping into ABVD and AVD groups according to bleomycin use. Data concerning the patient's characteristics, cancer type, and treatment plan were analyzed with proportion tests, Kaplan-Meier curves. univariate Cox regression, and χ 2 tests., Results: No discernible differences were found in this study between the overall survival and recurrence rate of patients treated with bleomycin compared to those without. Additionally, there was an increased risk of death in each subsequent cycle of chemotherapy of the complete ABVD protocol, demonstrating a risk of toxicity. Among the variables analyzed, hypertension and the presence of B symptoms were also associated with an increased risk of death, while the use of radiotherapy significantly improved survival., Conclusion: The results of this study suggest that bleomycin did not impact the outcome of Hodgkin's lymphoma treatment. Moreover, the increased risk of death associated with its toxicity during each cycle of treatment raises concerns about its role as an essential component of the gold standard for Hodgkin's lymphoma treatment. Therefore, further research and consideration are needed to reassess the use of bleomycin in Hodgkin's lymphoma treatment protocols., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of treatment de-escalation by omission of bleomycin from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for interim fluorodeoxyglucose positron emission tomography (iPET)-negative patients and assess efficacy and long-term safety for iPET-positive patients who underwent treatment intensification with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP/BEACOPP14). The median follow-up is 7.3 years. For all patients, the 7-year progression-free survival (PFS) and overall survival (OS) are 78.2% (95% CI, 75.6 to 80.5) and 91.6% (95% CI, 89.7 to 93.2), respectively. The 1.3% difference in 3-year PFS (95% CI, -3.0 to 4.7) between ABVD and doxorubicin, vinblastine, and dacarbazine (AVD) now falls within the predefined noninferiority margin. Among 172 patients with positive iPET, the 7-year PFS was 65.9% (95% CI, 58.1 to 72.6) and the 7-year OS was 83.2% (95% CI, 76.2 to 88.3). The cumulative incidence of second malignancies at 7 years was 5.5% (95% CI, 4.0 to 7.5) for those receiving ABVD/AVD and 2.5% (95% CI, 0.8 to 7.7) for those escalated to BEACOPP. With extended follow-up, these results confirm noninferiority of treatment de-escalation after a negative iPET. Escalation with BEACOPP for iPET-positive patients is effective and safe, with no increase in second malignancies.

Purpose: starting from a lack of precise and coherent data in literature, aim of this work is to retrospectively study the influence of chemotherapy with Temozolomide (TMZ) on a wide series of neuropsychological functions in a population of adult high-grade glioma patients., Methods: an extensive neuropsychological battery was administered pre-operatively (T0) and after 6 (T1) and 12 months (T2) from surgery. After full recovery from surgery, TMZ was delivered concomitant to radiotherapy and, subsequently, adjuvantly for 5-day cycles per month. Parametric and non-parametric analyses were conducted to verify the influence of several aspects of chemotherapy on the adjusted scores of each cognitive test at the two post-operative follow-ups., Results: Sixty-one patients were included at T0; patients with a lower adjuvant TMZ dosage reported a better performance at the visual attention test at T1, and at the deductive reasoning test at T2. Undergoing more than 8 cycles of adjuvant therapy was slightly associated with a better performance at the long-term verbal memory tasks at T2. No other associations were found with the other cognitive tests and autonomy scales administered., Conclusions: TMZ proved to be a secure treatment with no negative side effects on cognition and on level of daily autonomy, even at the highest dosage used. This is a positive finding which enables clinicians to reassure patients about the absence of significant negative effects of TMZ on their daily life functioning. In this view, eventual cognitive changes during treatment might not be attributed to chemotherapy but to other events such as tumour relapse., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Glioblastoma (GBM), WHO grade IV, is the most common primary malignant brain tumour among adults with a devastating overall survival of 14-22 months. Standard treatment of GBM includes maximum safe resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ), given over a period of approximately 9 months. Treatment and follow-up for Greenlandic patients with GBM are managed at Rigshospitalet (RH), Copenhagen. Greenlandic GBM patients, therefore, travel back and forth to RH, often unaccompanied, and challenged by cognitive failure or other symptoms from their disease and/or treatment. Few Greenlandic patients are diagnosed with GBM annually, but considering the poor prognosis and short remaining lifespan, it would be preferable to limit their travels. TMZ is administrated as capsules. Health personnel at Queen Ingrid's Hospital (DIH), Nuuk, are trained in treating other oncological diseases and handling side effects. Hence, it could be investigated whether administration of adjuvant TMZ at DIH could be feasible after personnel education as well as economic consideration and compensation, in close collaboration with neuro oncologists at RH. In this article, we describe the Greenlandic cancer treatment, and the typical workflow from diagnosis of GBM to treatment to progression.

Background: Temozolomide (TMZ) is an alkylating agent used to treat glioblastoma. However, the pharmacokinetics of TMZ to establish a treatment strategy for patients undergoing hemodialysis (HD) remain unclear. In this case report, we evaluated the pharmacokinetics and HD removal rate of TMZ in a patient with glioblastoma undergoing HD to determine optimal dosing of TMZ., Methods: A 78-year-old man with glioblastoma who underwent HD 3 times a week was treated with TMZ concomitant with radiotherapy. One dose of TMZ was prescribed at 75 mg/m 2 on the day before HD and another dose of 37.5 mg/m 2 on the day before non-HD. Peak and trough concentrations (1 hour and 12 hours after dosing, respectively) were evaluated before HD and on non-HD days. HD removal rate of TMZ was calculated based on the predialyzer and postdialyzer plasma concentrations. Furthermore, the TMZ plasma concentrations were measured using liquid chromatography-tandem mass spectrometry., Results: The mean plasma peak and trough concentrations ± SD after 75 mg/m 2 TMZ were 2917 ± 914 and 108 ± 17.6 ng/mL, respectively. Those after 37.5 mg/m 2 TMZ dosage were 1305 ± 650 and 53.8 ± 11.8 ng/mL, respectively. The mean HD TMZ removal rate was 84.9 ± 1.9%., Conclusions: TMZ was tolerable in patients undergoing HD. Based on the data from a single individual pharmacokinetic perspective, the pharmacokinetics of TMZ in this patient undergoing HD were comparable with those observed in patients with normal renal function. In addition, it may be reasonable to administer TMZ after HD because of the high HD removal rate., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Delobel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study aimed to systematically review and critically appraise cost-effectiveness studies on Brentuximab vedotin (BV) in patients with Hodgkin lymphoma (HL)., Methods: The PubMed, Scopus, Web of Science core collection, and Embase databases were searched until July 3, 2022. We included published full economic evaluation studies on BV for treating patients with HL. The methodological quality of the studies was assessed using the Quality of Health Economic Studies (QHES) checklist. Meanwhile, we used qualitative synthesis to analyze the findings. We converted the incremental cost-effectiveness ratios (ICERs) to the value of the US dollar in 2022., Results: Eight economic evaluations met the study's inclusion criteria. The results of three studies that compared BV plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) front-line therapy with doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) showed that BV is unlikely to be cost-effective as a front-line treatment in patients advanced stage (III or IV) HL. Four studies investigated the cost-effectiveness of BV in patients with relapsed or refractory (R/R) HL after autologous stem cell transplantation (ASCT). BV was not cost-effective in the reviewed studies at accepted thresholds. In addition, the adjusted ICERs ranged from $65,382 to $374,896 per quality-adjusted life-year (QALY). The key drivers of cost-effectiveness were medication costs, hazard ratio for BV, and utilities., Conclusion: Available economic evaluations show that using BV as front-line treatment or consolidation therapy is not cost-effective based on specific ICER thresholds for patients with HL or R/R HL. To decide on this orphan drug, we should consider other factors such as existence of alternative treatment options, clinical benefits, and disease burden., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Anthracyclines are associated with cardiotoxic manifestations that are mainly dose-dependent, with onset varying from a few days to many years after stopping treatment. Frequent monitoring for toxic manifestations, early detection, cessation of anthracycline use and appropriate treatment is the key to preventing morbidity and mortality. Complete heart block with doxorubicin use in Hodgkin's lymphoma is rarely reported, and is a severe toxic manifestation necessitating withdrawal or changing of regimen to etoposide + bleomycin + vinblastine + dacarbazine (EBVD), as in this case., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Preservation of fertility has become a growing concern in young females with Hodgkin lymphoma (HL). However, the rate of pregnancy after the current most frequently prescribed ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and darcarbazine) chemotherapy for HL has rarely been studied. In this study, we aim to determine the impact of ABVD on the fertility of women treated for HL. We conducted a noninterventional, multicenter study of female patients of childbearing age who were treated for HL. Two healthy apparied women nonexposed to chemotherapy (our controls) were assigned for each patient. Fertility was assessed by the number of pregnancies and births after HL treatment. Sixty-seven patients were included. The median age at diagnosis was 24.4 years (range, 16-43). HL was a localized disease for 68.7%. Of all the patients, 53.7% started at least 1 pregnancy after treatment vs 54.5% of the controls (P = .92). Of all the patients who desired children, 81% had at least 1 pregnancy. Patients treated with ABVD did not have a longer median time to pregnancy (4.8 years in the group of patients and 6.8 years for controls). Across patients, there were 58 pregnancies and 48 births (ratio, 1:2) and 136 pregnancies and 104 births (ratio, 1:3) for the control cohort. No increase in obstetric or neonatal complications has been reported in HL in our study. The number of pregnancies, births, and the time to start a pregnancy in young women treated with ABVD for HL is not different from that of controls. Therefore, females with HL treated with ABVD should be reassured regarding fertility., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The survival rate of adult patients with Hodgkin lymphoma (HL) depends on the responses to standard chemotherapy, radiotherapy, or combined therapy. Resource-limited countries face numerous obstacles in supporting patients with HL who undergo chemotherapy, especially in advanced stages., Aim: To analyze the survival outcomes of adult patients with HL after combined-modality treatment (CMT) with involved-field or non-involved-field radiotherapy., Methods and Results: We retrospectively reviewed the medical records of 90 adult patients with HL who received CMT at Rajavithi Hospital, Bangkok between 2007 and 2021. Patients with stage I-IV disease received different therapies depending on their risk group. The risk groups were evaluated according to initial response, bulky disease, and B symptoms. Patients (n = 90) who underwent CMT were followed up for 34.7 months (range, 1-141 months). The median follow-up periods of early and advanced-stage patients were 53.1 months and 23.5 months, respectively. The estimated 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with advanced-stage diseases were 85% and 62%, respectively. There was a difference in the 3-year overall survival among advance-stage patients who underwent ABVD (94%) compared to those administered BEACOPPesc (50%), and the 3-year PFS (84%) among patients who underwent ABVD was higher than that among those administered BEACOPPesc (66%). Radiotherapy increased toxicity but did not improve the survival rate., Conclusion: Chemotherapy administered to patients with advanced-stage adult HL was more effective than BEACOPPesc when ABVD was administered. Our findings are relevant for hospitals with limited resources., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Despite the advancements in multiagent chemotherapy in the past years, up to 10% of Hodgkin's Lymphoma (HL) cases are refractory to treatment and, after remission, patients experience an elevated risk of death from all causes. These complications are dependent on the treatment and therefore an increase in the prognostic accuracy of HL can help improve these outcomes and control treatment-related toxicity. Due to the low incidence of this cancer, there is a lack of works comprehensively assessing the predictability of treatment response, especially by resorting to machine learning (ML) advances and high-throughput technologies., Methods: We present a methodology for predicting treatment response after two courses of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy, through the analysis of gene expression profiles using state-of-the-art ML algorithms. We work with expression levels of tumor samples of Classical Hodgkin's Lymphoma patients, obtained through the NanoString's nCounter platform. The presented approach combines dimensionality reduction procedures and hyperparameter optimization of various elected classifiers to retrieve reference predictability levels of refractory response to ABVD treatment using the regulatory profile of diagnostic tumor samples. In addition, we propose a data transformation procedure to map the original data space into a more discriminative one using biclustering, where features correspond to discriminative putative regulatory modules., Results: Through an ensemble of feature selection procedures, we identify a set of 14 genes highly representative of the result of an fuorodeoxyglucose Positron Emission Tomography (FDG-PET) after two courses of ABVD chemotherapy. The proposed methodology further presents an increased performance against reference levels, with the proposed space transformation yielding improvements in the majority of the tested predictive models (e.g. Decision Trees show an improvement of 20pp in both precision and recall)., Conclusions: Taken together, the results reveal improvements for predicting treatment response in HL disease by resorting to sophisticated statistical and ML principles. This work further consolidates the current hypothesis on the structural difficulty of this prognostic task, showing that there is still a considerable gap to be bridged for these technologies to reach the necessary maturity for clinical practice., (© 2023. The Author(s).)

Background: Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been regarded as the standard treatment regimen for classical Hodgkin lymphoma. In recent years, ABVD-like regimens, which emerged due to shortages and the lung toxicity of bleomycin or the emergence of immune checkpoint inhibitors and antibody-drug conjugates, may be favorable, but have not yet been tested., Methods: We compared the outcomes of ABVD with ABVD-like regimens, which include bleomycin was completely or partially omitted; meanwhile, etoposide or PD-1 inhibitors were added., Results: 5-Year progression-free survival (PFS) was higher for ABVD than ABVD-like regimens in young patients (82.1% vs. 67.0%, p = 0.029), patients with serum beta-2 microglobulin (β2-MG) ≥ 1.85 mg/L (75.8% vs. 57.6%, p = 0.046), and advanced-stage patients with IPS score 4-7(63.1%, 18.3%, p = 0.038). For elderly (60.5% vs.76.1%, p = 0.089), patients with β2-MG < 1.85 mg/L (83.1% vs 76.1%, p = 0.282), and advanced-stage patients with IPS score 0-3(84.6% vs. 81.3%, p = 0.476), 5-year PFS for ABVD did not differ from ABVD-like regimens. Elderly patients treated with bleomycin-free regimens showed a better survival trend compared with ABVD (99.3% vs. 61.3%, p = 0.270)., Conclusion: ABVD is superior to ABVD-like regimens in achieving PFS in young patients or patients with poor prognosis including high IPS score and β2-MG level. ABVD-like regimens are as effective as ABVD in elderly or low-risk patients including low IPS score and β2-MG level; elderly patients treated with bleomycin-free regimens exhibit a better survival trend compared with ABVD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The goal of the research was to investigate if a combination of vincristine, irinotecan and temozolomide (VIT) could benefit adult patients with metastatic Ewing sarcoma who had already been heavily pretreated. Metastatic Ewing sarcoma patients had their data retrospectively analyzed. The patients' clinical, radiological and therapeutic data were recorded. Survival analyzes were performed with these data. The study enlisted the participation of sixteen patients. The average age was 25 years old (range: 20-42). The lung was the most prevalent metastatic location (81.3%). Patients had received at least two distinct chemotherapy combinations (87.5%) and palliative radiotherapy (37.5%) before receiving the (VIT) combination. The Median progression-free survival time was found as 3.4 (95% CI, 1.8-4.9) months. Five patients (31.3%) experienced a partial response, while the remaining patients (68.7%) had progressing disease. Thirteen individuals (81.3%) had grade 1-2 adverse events, whereas five (31.3%) had grade 3-4 adverse events. Hematological complications were the most common side effects (87.5%). Median overall survival was calculated as 5.6 (95% CI, 3.6-7.5) months in the patients after the beginning of VIT regimen. We demonstrated the efficacy of the VIT regimen in adult patients with metastatic Ewing sarcoma in this research. In these extensively pretreated patients, toxicities were a concern. Metastatic Ewing sarcoma patients have few treatment choices. In patients who have had a good performance status, VIT regimen may be considered for disease control.

FRONTLINE THERAPY FOR CLASSICAL HODGKIN LYMPHOMA PATIENTS. Upfront first-line chemotherapy is indicated for all features of classical Hodgkin's lymphoma, followed by involved node radiotherapy in early stages; the ABVD protocol (doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine) is the international standard of care. The 7-agent BEACOPP protocol (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone) is used in advanced stages in its «escalated» version (BEAesc). During the 2010 decade, it has been demonstrated that strategies guided by positron emission tomography (PET) allows optimizing the benefit/risk ratio of the treatment by decreasing the intensity of therapies for good responders and intensifying treatment of poor responders. Thus, early PET response evaluation is now essential to adapt the treatment intensity. Despite these major advances, several issues remain, including the management of acute and long-term side effects of first-line treatments, the better options for refractory patients, the place and optimization of radiotherapy, and the place for new therapeutic agents such as the anti-CD30 conjugate antibody (brentuximab vedotin) and PD-1 inhibitors in the first-line treatment setting., Competing Interests: C. Rossi déclare avoir été pris en charge à l’occasion de déplacement pour congrès par Takeda, Roche, Kyte, Sanofi. O. Casasnovas déclare avoir participé à des interventions ponctuelles pour Roche, Takeda, Merck, BMS et avoir été pris en charge à l’occasion de déplacement pour congrès par Roche, Gilead, Incyte Biosciences, ADC Therapeutics, Janssen, AbbVie.

ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269)., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: The optimal dose schedule of vincristine, irinotecan, and temozolomide (VIT) in relapsed or refractory patients with Ewing sarcoma requires clarification., Patients and Methods: Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter d × 5 schedule (irinotecan 50 mg/m2/d D1-5, vincristine 1.4 mg/m2 D1) or protracted d × 5×2 schedule (irinotecan 20 mg/m2/d D1-5,8-12, vincristine 1.4 mg/m2 D1,8) together with temozolomide (100 mg/m2/d D1-5). Patients were treated every 3 weeks for up to eight cycles until progression or unacceptable toxic effects occurred. The primary endpoint was objective response rate at 12 weeks (ORR12w). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety., Result: A total of 46 patients presenting with relapsed or refractory Ewing sarcoma were randomly assigned to the d × 5 (n = 24) or d × 5×2 (n = 22) schedules. Median follow-up was 10.7 months in the d × 5 group and 8.3 months in the d × 5×2 group. ORR12w was lower for d × 5 (5/24; 20.8%) patients than for d × 5×2 (12/22; 54.5%; P = 0.019), but no significant difference was found in PFS (median PFS, 2.3 months for d × 5 vs. 4.3 months for d × 5×2) or OS (median OS, 14.8 months for d × 5 and 12.8 months for d × 5×2). Patients receiving the d × 5 schedule reported more grade 3 and 4 adverse events (AE) than those receiving d × 5×2, including diarrhea/abdominal pain and vomiting/nausea., Conclusions: The protracted d × 5×2 VIT schedule showed superior efficacy and favorable tolerability compared with the shorter d × 5 VIT schedule in patients with relapsed or refractory Ewing sarcoma., (©2023 American Association for Cancer Research.)

Despite the burden of anemia among Hodgkin lymphoma (HL) patients, data evaluating red cell concentrate transfusion are limited. We retrospectively studied 285 newly diagnosed HL patients who received first-line adriamycin, bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD) treatment at Groote Schuur Hospital, Cape Town. HIV prevalence in the cohort was 39.5% and 74.2% of patients had advanced stage HL. Patient prognosis was scored using the HL International Prognostic Score (IPS-7) and HL IPS-3. Seventy (24.6%) patients were transfused with a median of 2 (IQR 1-5) units per patient. Compared to HIV-negative patients, more HIV-positive patients were transfused (14.1% vs. 40.4%, p  < .001) and received more units, median 2 (IQR 1-3) vs. 3 (IQR 2-5), p  = .035. HL IPS-7 (OR 2.1, p  < .001) and HL IPS-3 (OR 2.6, p  < .001) were independently associated with transfusion. HL IPS-7, HL IPS-3, and HIV positivity remained associated with transfusion after adjusting for covariates. For patients with newly diagnosed HL, HL IPS-7, HL IPS-3, and HIV status predicted transfusion.

Objectives: Our study aimed to assess the benefit of prolonging adjuvant temozolomide (TMZ) therapy beyond 6 cycles in glioblastoma multiform patients., Materials and Methods: The medical records of 329 patients in 2 cancer centers in Egypt were reviewed from January 2008 to December 2018 who were diagnosed with diffuse gliomas. Data were collected on patient demographics, presenting complaints, tumor size, treatment modalities (extent of surgery, radiotherapy dose and technique, concomitant TMZ, and the number of adjuvant TMZ cycles), and reported adverse events., Results: In the studied cohort, 105 patients were treated with adjuvant TMZ, 33 patients received <6 cycles (TMZL), 41 patients received the standard 6 cycles (TMZS), and 31 patients received >6 cycles (TMZE). Our results showed the median overall survival in the TMZL arm was 8.47 months compared with 15.83 months in the TMZS arm and 27.33 months in the TMZE arm ( P < 0.001). Furthermore, a median progression-free survival of 6.35 months was reported in the TMZL group versus, 12.7 and 22.90 months in (TMZS) and (TMZE) groups, respectively( P < 0.001). In the multivariate analysis, the extended adjuvant TMZ with a hazard ratio of 3.106 (95% CI: 2.43-14.46; P < 0.001) was statistically significantly associated with a better outcome., Conclusions: Extended adjuvant TMZ therapy beyond 6 cycles may significantly improve the progression-free survival and overall survival in patients with glioblastoma multiform., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the investigator-sponsored randomized phase II NIVAHL trial for early-stage unfavorable classical Hodgkin lymphoma (HL), two schedules of four cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine followed by 30 Gy involved-site radiotherapy resulted in high complete remission rates and an unprecedented 1-year progression-free survival in 109 patients. In this article, we report the preplanned final analysis conducted three years after the registration of the last patient including long-term safety results. No survival events were observed since the primary analysis, and after a median follow-up (FU) of 41 months, the overall survival was 100% in both treatment groups. The progression-free survival was 98% and 100% in the sequential and concomitant nivolumab, doxorubicin, vinblastine, and dacarbazine treatment groups, respectively. At last FU, the mean forced expiratory pressure in one second was 95.5% (standard deviation 12.7%), the mean diffusion capacity for carbon monoxide adjusted for hemoglobin was 82.8% (standard deviation 15.4%), and the left ventricular ejection fraction was in the normal range in 95% of patients. Hypothyroidism requiring long-term medication occurred in 15% of patients, who were nearly exclusively female (87%). No second primary malignancies occurred, and no patient required corticosteroid treatment at last FU. Patient-reported normalized global quality-of-life score measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 improved over time. This preplanned FU analysis of the largest anti-programmed death protein 1 HL first-line trial to date confirms the outstanding efficacy and relatively favorable safety profile of this therapeutic approach.

Aims: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O 6 -methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens., Materials and Methods: LARC patients with clinical stage II (cT3-4N0) or III (cT any N+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate., Results: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events., Conclusion: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Abstract: Temozolomide (TMZ) is an alkylating chemotherapeutic drug, often used in high-grade glioma and metastatic melanoma. Common side effects of this include myelosuppression and gastrointestinal side effects. Vitiligo-like reaction is extremely rare after TMZ. Here, we report a case of a 55-year-old patient of glioblastoma who developed vitiligo-like reaction after starting adjuvant TMZ., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Purpose: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population., Methods: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy., Results: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE., Conclusion: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures., Trial Registration: NCT01149109., (© 2023. The Author(s).)

Background: The main goal of our study is to comparatively evaluate outcomes of hypofractionation and long-term fractionation with temozolomide (TMZ) in glioblastoma patients older than 65 years., Methods: Eighty patients with glioblastoma meeting the eligibility criteria of >65 years of age, the Karnofsky performance score (KPS) >60, no previous radiotherapy (RT) to the brain referred to our department between October 2009 and October 2016 for adjuvant chemoradiotherapy after surgery were studied. The first group of patients received a dose of 6000 cGy in 30 fractions and the second group was delivered 4000 cGy in 15 fractions All patients used TMZ concomitantly with RT. We used the paired t-test and the Wilcoxon signed-rank test with Statistical Package for the Social Sciences, version 15.0 (SPSS, Inc., Chicago, IL, USA) software for statistical analysis., Results: Forty-six patients were men (57.5%), and 34 patients (42.5%) were woman. Median age was 68 years (range 66-87). Median KPS was 75 (range 60-100). Median follow-up time was 12 months (range 6-30). Median overall survival was 15.2 months and 14.3 months for patients with hypofractionation and conventional fractionation, respectively, with no statistical significance (P = 0.13)., Conclusion: Hypofractionation should be recommended to the elderly glioblastoma patients older than 65 years because of the short treatment time, reduced acute adverse effects of both TMZ and RT compared to long-term fractionation., Competing Interests: None

Purpose: Temozolomide (TMZ), a cytotoxic DNA alkylating agent, is the main chemotherapy used for the treatment of high grade astrocytomas. The active alkylator, methylhydrazine, is not recovered in urine and thus renal function is not expected to affect clearance. Prescribing information for TMZ states pharmacokinetics have not been studied in adults with poor renal function, eGFR < 36 mL/min/1.73 m 2 . We reviewed our clinical experience with TMZ in patients with impaired renal function to evaluate safety of administering full dose TMZ., Methods: The primary endpoint was to characterize the incidence and severity of thrombocytopenia in patients with eGFR < 60 mL/min/1.73 m 2 who received TMZ for treatment of high grade gliomas (HGG) or primary CNS lymphoma (PCNSL). Secondary endpoints included incidence and severity of neutropenia, lymphopenia hepatotoxicity, and number of TMZ cycles administered. Medical records of patients with HGG or PCNSL treated with TMZ from October 1, 2016-September 30, 2019 were accessed to identify cases for this study., Results: Thirty-two patients were eligible for this study. Of the seven patients with eGFR < 36 mL/min/1.73m 2 , 38/39 cycles (97%) were completed without grade 3-4 thrombocytopenia. No patients experienced grade 3-4 neutropenia, and grade 3-4 lymphopenia occurred in 5 cycles (15%). One patient discontinued TMZ 7 days prior to completion of radiation due to thrombocytopenia., Conclusion: Hematologic toxicity in patients with severe renal dysfunction, eGFR < 36 mL/min/1.73m 2 , is similar to that of patients with normal renal function. Severe renal impairment does not preclude use of temozolomide, but cautious monitoring of blood counts is warranted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To investigate the current variability in radiotherapy practice for elderly glioblastoma patients., Methods: A questionnaire comprising general information on elderly glioblastoma, treatment selection, radiotherapy and 16 clinical case-scenario-based questions (based on age, performance, extent of resection and MGMT promoter methylation) was sent to brain tumor radiation oncologists., Results: Twenty-one responses were recorded. Most (71.4%) stated that 70 years is an adequate cut-off for 'elderly' individuals. The most preferred hypofractionated short-course radiotherapy schedule was 40-45 Gy over 3 weeks (81.3%). The median margin for high-dose target volume was 5 mm (range, 0-20 mm) from the T1-enhancement for short-course radiotherapy. The case-scenario-based questions revealed a near-perfect consensus on 6-week standard radiotherapy plus concurrent/adjuvant temozolomide as the most appropriate adjuvant treatment in good performing patients aged 65-70 years, regardless of surgery and MGMT promoter methylation. Notably, in 75-year-old patients with good performance, the most preferred treatment was 6-week radiotherapy (81.0-90.5%) plus concurrent/adjuvant temozolomide (71.4-95.2%) rather than short-course radiotherapy or radiotherapy alone. Although the use of 3-week short-course radiotherapy increased with age and decreased performance status (all P < 0.05), 6-week radiotherapy was adopted in a significant proportion of responders (14.3-23.8%) even for wheelchair-bound, 75-year-old patients. Temozolomide use was affected by age, performance and MGMT promoter (all P < 0.05)., Conclusions: A high level of consensus was observed in treating elderly glioblastoma patients with good performance status. However, the variability increased, especially for older patients and those with poor performance. This study serves as a basis for designing future clinical trials in elderly glioblastoma., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available., Methods: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed., Results: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up., Conclusions: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.)., (Copyright © 2022 Massachusetts Medical Society.)

COVID-19 pandemic revolutionized the way in which cancer patients are treated worldwide. Regarding neuro-oncological patients, usually considered frail and with lower life-expectancy in respect to other oncological patients, the international scientific community had to urgently reorganize the treatment approach in order to minimize the risk of in-hospital contagious. For GBM patients, adjuvant treatments have been evaluated with even much more attention with regard to the expected efficacy. As a consequence, an hypofractioned radiotherapy regimen has been preferred in order to reduce the daily hospital accesses and, especially in pMGMT unmethylated patients, chemotherapy with Temozolomide was avoided. Here, we made a comprehensive evaluation of the neurooncological community suggestions regarding GBM treatment in the pre-vaccine era of COVID-19 pandemic.

Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs. <60 years) was a pre-specified subgroup analysis; as the ECHELON- 1 study was not powered for these analyses, reported P-values are descriptive. Of 1,334 enrolled patients, 186 (14%) were aged ≥60 years (A+AVD: n=84, ABVD: n=102); results below refer to this age group. Modified progression-free survival per independent review facility was similar in the two arms at 24 months (A+AVD: 70.3% [95% confidence interval (CI): 58.4-79.4], ABVD: 71.4% [95% CI: 60.5-79.8], hazard ratio (HR)=1.00 [95% CI: 0.58-1.72], P=0.993). After a median follow-up of 60.9 months, 5-year progression-free survival per investigator was 67.1% with A+AVD versus 61.6% with ABVD (HR=0.820 [95% CI: 0.494-1.362], P=0.443). Comparing A+AVD versus ABVD, grade 3/4 peripheral neuropathy occurred in 18% versus 3%; any-grade febrile neutropenia in 37% versus 17%; and any-grade pulmonary toxicity in 2% versus 13%, respectively, with three (3%) pulmonary toxicity-related deaths in patients receiving ABVD (none in those receiving A+AVD). Altogether, A+AVD showed overall similar efficacy to ABVD with survival rates in both arms comparing favorably to those of prior series in older patients with advanced-stage classical Hodgkin lymphoma. Compared to ABVD, A+AVD was associated with higher rates of neuropathy and neutropenia, but lower rates of pulmonary-related toxicity. Trials registered at ClinicalTrials.gov identifiers: NCT01712490; EudraCT number: 2011-005450-60.

This multi-centric prospective study (InPOG-HL-15-01) assessed epidemiological, clinical and outcome data of advanced stage Hodgkin Lymphoma (IIB, III and IV) in children and adolescents ( N  = 262). Chemotherapy regimen was ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and radiotherapy (RT) was restricted to patients with bulky disease at diagnosis or with suboptimal response at early response assessment (ERA). ERA revealed complete response in 175 (68.1%), partial response in 77 (29.9%), stable disease in 2 (0.8%), and progressive disease in 3 (1.2%) patients. RT was administered to 111 (97 bulky disease, 14 suboptimal response) patients. Five-year event free (EFS) and overall survival for the whole cohort was 81.1% and 90.8% respectively. On multivariate analysis, the only statistically significant predictor of EFS was use of RT (89% versus 74.2%; p -value <0.001). This study reinforces the benefit of consolidative RT in bulky disease and in those with suboptimal response at ERA on an ABVD backbone.

Background: The prognosis of patients with relapsed Ewing sarcoma is poor. In this study, we aimed to pooled-analyze the efficacy and safety of the combination of irinotecan and temozolomide in treating patients with relapsed Ewing sarcoma., Methods: PubMed, Cochrane CENTRAL, Web of Science, and EMBASE were systematically searched on September 27, 2021. The primary outcomes were rates of objective response and disease control, and the secondary outcomes were toxicities., Results: Six retrospective studies with 184 patients were enrolled in the analysis. The median age ranged from 14 to 21. The integrated rates were 44% (95% confidence interval [CI] 31-58) for objective response and 66% (55-77) for disease control. Grade 3-4 neutropenia, thrombocytopenia, and diarrhea occurred in 8% (3-16), 7% (3-11), and 8% (5-10) of chemotherapeutic cycles, respectively. 18% (7-32) and 6% (2-11) of patients suffered grade 3-4 neutropenia and thrombocytopenia after irinotecan plus temozolomide treatment., Conclusion: Irinotecan plus temozolomide combination chemotherapy showed antitumor activity and an acceptable safety profile in patients with relapsed Ewing sarcoma. More future prospective studies are needed to confirm the retrospective results., (© 2022. The Author(s).)

Introduction: While Hodgkin lymphoma (HL) is mostly curable, outcomes for advanced-stage HL remain unsatisfactory. The International Prognostic Score and its modifications were developed to predict HL prognosis; however, more straightforward prognostic factors are needed. This study aimed to identify simpler prognostic factors for advanced-stage newly diagnosed HL (NDHL)., Methods: This retrospective study used the Taiwan National Health Insurance Research Database and the Taiwan Cancer Registry. Patients with advanced-stage NDHL receiving ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or ABVD-like regimens between 2009 and 2016 were enrolled. Cox proportional hazards models were used to identify prognostic factors for the time to next treatment (TTNT) and overall survival (OS). We used the time-dependent area under the receiver operating characteristic curve (AUROC) to evaluate model performance., Results: The study included 459 patients with advanced-stage NDHL. A bimodal age distribution (peaks 20-44 and >65 years) was observed. Over a median follow-up of 4.7 years, the complete remission and OS rates were 52% and 76%, respectively. Age ≥60 years (adjusted hazard ratio [aHR]: 1.73, 95% confidence interval [CI]: 1.23-2.43), extranodal involvement (1.40, 1.05-1.87), B symptoms (1.53, 1.13-2.06), and Charlson Comorbidity Index (CCI) ≥1 (1.49, 1.08-2.06) were significantly associated with a shorter TTNT. The time-dependent AUROC was .65. With a time-dependent AUROC of .81, age ≥60 years (4.55, 2.90-7.15) and CCI ≥1 (1.86, 1.18-2.91) were risk factors for worse OS., Conclusion: Older age and more comorbidities were risk factors for an inferior OS in advanced-stage NDHL, while older age, extranodal involvement, B-symptoms, and higher CCI were significantly associated with disease relapse.

The outcome of patients with Hodgkin lymphoma (HL) has improved significantly in recent years, and now attention is increasingly being focused on the well-being of these young patients. This study aimed to analyse the influence of HL and its treatment on the spermatogenic status of 46 male HL patients with available spermiograms, treated between 2008 and 2016. Analysing prognostic factors at diagnosis, we found that the number of spermatozoa was reduced in stage III-IV; motility and vitality were reduced in stage III-IV and in the presence of B symptoms; and abnormal forms were increased in patients with elevated erythrocyte sedimentation rate (ESR) and low albumin. Furthermore, we found that haematopoietic stem cell transplantation (HSCT) was associated with a severe impairment of fertility in terms of sperm motility. In HL-treated patients who did not undergo HSCT we found a statistically significantly improved fertility in terms of motility. In this study, we found that HSCT induced infertility in the majority of male patients with HL, but that first-line treatment could improve the impaired fertility status caused by disease. Further studies are needed in larger case series to investigate risk factors for impaired fertility at HL diagnosis and after treatment., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: ABVD (doxorubicin, bleomycin,vinblastine, and dacarbazine) is not a standard regimen in children due to concerns regarding late effects. However, no studies have evaluated long-term toxicities of ABVD in children., Methods: Total 154 pediatric Hodgkin lymphoma (HL) survivors uniformly treated with ABVD were clinically followed up as per institutional protocol. All participants were evaluated for cardiac, pulmonary, and thyroid function abnormalities by multigated acquisition scan (MUGA) scan, spirometry with diffusion capacity of lung for the uptake of carbon monoxide (DLCO), and thyroid profile test, respectively, at a single time point. Predictors of toxicity were also analyzed., Results: The median duration of follow-up of the cohort was 10.3 years (6.04-16.8). No secondary malignant neoplasm (SMN) or symptomatic cardiac/pulmonary toxicities were detected. Nine patients (5.9%) had left ventricular ejection fraction (LVEF) <55%. Subclinical and overt hypothyroidism were observed in 78 (50.6%) and 16 (10.4%) survivors, respectively. Abnormal spirometry and reduced DLCO was observed in 43.2% and 42.0% survivors, respectively. Receiving neck radiation was significantly associated with thyroid dysfunction (odds ratio [OR] 16.04, p < .001); age ≥10 years predicted reduced DLCO (OR 4.12, p = .001). Sixty-three and 33 patients had one and two late adverse effects, respectively; receiving neck radiation predicted development of multiple late effects (proportional OR 4.72, p < 0.001). Cumulative dose of chemotherapy did not predict toxicity., Conclusions: Overall, ABVD appears safe in children at a relatively short follow-up. Long-term safety data are required before it can be adopted for treating pediatric HL patients. Children receiving neck radiation require close follow-up., (© 2021 Wiley Periodicals LLC.)

Background: Malignant gliomas (MG) are aggressive brain tumours in adults. The standard of care is concurrent radiation plus temozolomide (TMZ) [chemo-radiotherapy (CRT)] followed by TMZ maintenance up to 6 months. TMZ is considered to have a low toxicity profile, but several studies reported occurrence of severe myelosuppression, especially during the concomitant phase. Toxicity may be prolonged, thus treatment should be discontinued., Purpose: To evaluate the risk of recurrente myelotoxicity during adjuvant chemotherapy (CT) in patients who recovered from severe myelotoxicity during CRT., Methods: We retrospectively collected data on patients with MG who developed and recovered from severe myelotoxicity during CRT from eight Italian neuro-oncology centers., Results: We included 87 patients. Histology was Glioblastoma (GBM) in 78 patients (89.7%); 60% of patients were female. After myelotoxicity recovery, 54 (62%) received treatment. The majority of them (82%, n = 44) received adjuvant TMZ and 18% (n = 10) others treatments. Out of 44 patients who received adjuvant TMZ, 34% experienced the re-occurrence of grade 3-4 myelotoxicity which required permanent CT discontinuation in 6 (13%) cases. Patients who received TMZ or other treatments had longer overall (OS) (adjusted HR 0.46, p = 0.008) and progression free survival (PFS) (adjusted HR 0.57, p = 0.034) than those who remained untreated., Conclusion: Our study suggests that after severe myelotoxicity the majority of patients received treatment, particularly with TMZ. Only a fraction of patients experienced toxicity recurrence, suggesting that TMZ is well tolerated and had an impact on PFS and OS., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Liposarcomas are rare tumors arising from adipocytic tissue and accounting for approximately 15-20% of all soft tissue sarcomas. Liposarcoma can be further classified into histopathological subtypes with variable chemosensitivity according to subtype. Decisions regarding management should be made on an individual basis, but surgery for localized disease and systemic chemotherapy remain the mainstay of treatment. Currently, only doxorubicin and trabectedin have robust Phase III data to support their use in the management of advanced liposarcoma. However, in the subgroup analysis of a Phase III trial comparing eribulin with dacarbazine, there was a greater than 7-month improvement in median overall survival in those treated with eribulin. There are also promising results from emerging studies in novel and targeted agents for the treatment of liposarcoma.

Purpose: To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma., Patients and Methods: This two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden., Results: Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom burden worsened at cycle 2 but stabilized by cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12-24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. Pharmacokinetic/pharmacogenomic analyses revealed that the CYP1A2&#95;5347T>C (rs2470890) polymorphism was associated with higher AUC inf value., Conclusions: Zotiraciclib combined with temozolomide is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib., (©2021 American Association for Cancer Research.)

Purpose: Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males., Methods: The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels., Results: Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis., Conclusions: ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.