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Journal of Clinical Oncology : Official... Jan 2024JCO The primary analysis of the Early positron emission tomography (ePET) Response-Adapted Treatment in localized Hodgkin Lymphoma H10 Trial demonstrated that in... (Randomized Controlled Trial)
Randomized Controlled Trial
JCO The primary analysis of the Early positron emission tomography (ePET) Response-Adapted Treatment in localized Hodgkin Lymphoma H10 Trial demonstrated that in ePET-negative patients, the risk of relapse increased when involved-node radiotherapy (INRT) was omitted and that in ePET-positive patients, switching from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) significantly improved 5-year progression-free survival (PFS). Here, we report the final results of a preplanned analysis at a 10-year follow-up. In the favorable (F) ePET-negative group, the 10-year PFS rates were 98.8% versus 85.4% (hazard ratio [HR], 13.2; 95% CI, 3.1 to 55.8; value for noninferiority = .9735; difference test < .0001) in favor of ABVD + INRT; in the unfavorable (U) ePET-negative group, the 10-year PFS rates were 91.4% and 86.5% (HR, 1.52; 95% CI, 0.84 to 2.75; value for noninferiority = .8577; difference test = .1628). In ePET-positive patients, the difference in terms of PFS between standard ABVD and intensified BEACOPPesc was no longer statistically significant (HR, 0.67; 95% CI, 0.37 to 1.20; = .1777). In conclusion, the present long-term analysis confirms that in ePET-negative patients, the omission of INRT is associated with lower 10-year PFS. Instead, in ePET-positive patients, no significant difference between standard and experimental arms emerged although intensification with BEACOPPesc was safe, with no increase in late adverse events, namely, second malignancies.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Disease-Free Survival; Doxorubicin; Follow-Up Studies; Hodgkin Disease; Neoplasm Recurrence, Local; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 37967311
DOI: 10.1200/JCO.23.01745 -
Case Reports in Oncology 2023Most elderly patients with tuberculosis (TB) have previously been infected with , which remains dormant in the body for decades and may reactivate when their immunity...
Most elderly patients with tuberculosis (TB) have previously been infected with , which remains dormant in the body for decades and may reactivate when their immunity declines due to underlying diseases. Elderly cancer patients are at a high risk for TB, and the treatment of TB reactivation in these patients is challenging. Among cancer patients, the incidence of TB reactivation is the highest in lymphoma patients. However, the impact of chemotherapy on TB reactivation in lymphoma patients is unknown. We report the case of an immunocompetent elderly patient with primary central nervous system lymphoma (PCNSL) having no prior history of TB, who developed miliary TB during multiagent chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine (R-MPV therapy). Retrospectively, the chest computed tomography showed calcification of the pleura, suggesting that the patient had a latent tuberculosis infection (LTBI) and developed miliary TB from the reactivation of TB triggered by the R-MPV therapy. Our case emphasizes that when chemotherapy is administered to patients with PCNSL, interferon-gamma release assay (IGRA) should be performed if there are findings on chest examination suggestive of LTBI, such as pleural calcification, and if IGRA is positive, chemotherapy should be given concurrently with LTBI treatment.
PubMed: 37900802
DOI: 10.1159/000530711 -
Pharmaceutics Sep 2023The present study aimed to evaluate the stability of active pharmaceutical ingredients (APIs) from different pharmacological classes in a compounded oral suspending...
The present study aimed to evaluate the stability of active pharmaceutical ingredients (APIs) from different pharmacological classes in a compounded oral suspending vehicle. Oral suspensions of amoxicillin trihydrate (50 mg/mL), clozapine (25 mg/mL), indomethacin (5.0 mg/mL), levodopa/carbidopa (10.0/2.5 mg/mL), levothyroxine sodium (T4, 25 µg/mL), lomustine (4.0 and 10.0 mg/mL), methyldopa (25 mg/mL) and procarbazine (10.0 mg/mL) were formulated in SyrSpend SF PH4 and the stability was monitored for up to 90 days, except for amoxicillin trihydrate, which was evaluated for 30 days only. The APIs' stability was determined by measuring percent recovery using stability-indicating high-performance liquid chromatography (HPLC or UHPLC) or titration (amoxicillin trihydrate only). The stability of amoxicillin trihydrate, clozapine, indomethacin and levodopa/carbidopa were studied at both refrigerated (2-8 °C) and room temperature (20-25 °C). Lomustine, procarbazine, and methyldopa were studied at refrigerated temperature only. Our data demonstrated promising stability for the compounded suspensions containing various APIs, investigated in SyrSpend SF PH4, as all APIs exhibited stability throughout the study duration and met content uniformity criteria. These findings lead to the conclusion that the tested compounded oral suspensions present a viable approach for creating personalized, age-appropriate formulations. The capacity to ensure dose consistency and stability using APIs from diverse pharmacological classes renders them suitable choices for both pediatric and geriatric patients.
PubMed: 37896148
DOI: 10.3390/pharmaceutics15102388 -
Journal of Clinical Oncology : Official... Jan 2024JCO 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...
JCO 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.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Follow-Up Studies; Hodgkin Disease; Neoplasms, Second Primary; Prednisone; Vinblastine; Vincristine
PubMed: 37883739
DOI: 10.1200/JCO.23.01177 -
Journal of Neurosurgery. Case Lessons Oct 2023High-grade gliomas are aggressive primary brain tumors, the most common of which is glioblastoma multiforme. Despite advances in treatment, the prognosis for these...
BACKGROUND
High-grade gliomas are aggressive primary brain tumors, the most common of which is glioblastoma multiforme. Despite advances in treatment, the prognosis for these patients remains poor. The most common chemotherapeutic agents used in the treatment of this pathology include temozolomide (TMZ), procarbazine, lomustine, and vincristine. It is unclear whether chemotherapy should be held during resection for high-grade gliomas, because the perioperative risk profile is not clearly defined.
OBSERVATIONS
The authors report a case series of 18 surgeries to investigate the effects of concurrent TMZ and lomustine chemotherapy on surgical complications in patients undergoing repeat resection for recurrent high-grade gliomas. The authors found no postoperative infections, self-limiting postoperative complications, or excessive intraoperative blood loss and found one intraoperative complication.
LESSONS
There may not be a need to pause TMZ and lomustine chemotherapy during recurrent resections for high-grade gliomas, and continuing these medications throughout the perioperative period may be appropriate. This case series suggests that patients receiving TMZ and lomustine chemotherapy who need a repeat resection for recurrent high-grade gliomas should consider remaining on their chemotherapy regimen because it has been shown in the literature to improve recurrence-free survival time.
PubMed: 37870760
DOI: 10.3171/CASE23341 -
No Shinkei Geka. Neurological Surgery Sep 2023Oligodendrogliomas were clearly defined as tumors with IDH mutations and 1p/19q codeletion by the World Health Organization(WHO)in 2016. Their prognosis is better than...
Oligodendrogliomas were clearly defined as tumors with IDH mutations and 1p/19q codeletion by the World Health Organization(WHO)in 2016. Their prognosis is better than that of morphologic oligodendrogliomas, which might include some other gliomas according to WHO in 2016 and 2021. The term "low-grade gliomas" does not exist in the WHO classification and has changed in meaning over time; prior to WHO 2016, it meant grade I and II gliomas; subsequently, it changed to "lower-grade gliomas," including grade II and III gliomas, with the same molecular features. In the current classification, IDH wild-type grade II and III gliomas have been eliminated, and "lower-grade gliomas" now only include gliomas with IDH mutations. Maximal safe resection is necessary for a proper molecular diagnosis and survival, and awake craniotomy should be aggressively considered to prevent permanent postoperative neurologic deficits for tumors in the eloquent region. Supramarginal resection is an attractive approach for neurosurgeons to improve survival outcomes, but the evidence is still lacking. Chemoradiotherapy with procarbazine, CCNU, and vincristine is recommended for both grade 2 and 3 oligodendrogliomas. However, the risk of radiation-induced neurotoxicity is a concern in long-term survivors, and several clinical trials have tested the efficacy of chemotherapy alone in terms of cognitive function. Since CCNU is not approved in Japan, ACNU-containing regimen as PAV, or temozolomide are commonly used for the tumor.
Topics: Humans; Oligodendroglioma; Glioma; Cognition; Mutation; Lomustine
PubMed: 37743332
DOI: 10.11477/mf.1436204822 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
World Neurosurgery Nov 2023This study aimed to investigate the effectiveness and safety of various adjuvant regimens in patients with low-grade gliomas and to further explore the optimal adjuvant... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to investigate the effectiveness and safety of various adjuvant regimens in patients with low-grade gliomas and to further explore the optimal adjuvant treatment for patients with low-grade gliomas and the differences in the efficacy of each treatment regimens in different tumor types.
METHODS
A comprehensive search of the PubMed, Cochrane Library, Ovid, Embase, and Web of Science databases was conducted to screen randomized and nonrandomized controlled trials related to adjuvant therapy in patients with low-grade gliomas. The Cochrane quality assessment method and the Newcastle-Ottawa Scale were used to assess the quality of the included randomized and nonrandomized controlled trials, respectively. The data from previous studies were extracted using Excel and GetData Graph Digitizer 2.26 software, and network meta-analysis was performed using RevMan 5.3 and Stata 16.0 statistical software.
RESULTS
The specific ranking of 5-year progression-free survival (5-year PFS) for each treatment regimen from the best to the worst in patients with low-grade gliomas was surgery (S) combined with procarbazine, lomustine, and vincristine (S + PCV); surgery combined with standard radiotherapy and PCV multidrug chemotherapy (S + RT + PCV); surgery combined with standard radiotherapy and temozolomide monotherapy (S + RT + TMZ); surgery combined with enhanced radiotherapy (S + H-RT); surgery combined with standard radiotherapy (S + RT); surgery combined with TMZ (S + TMZ); and S. The 5-year overall survival (OS) ranking was S + RT + TMZ, S + RT + PCV, surgery combined with enhanced radiotherapy and TMZ monotherapy (S + H-RT + TMZ), S + H-RT, S + RT, and S. The 2-year progression-free survival ranking was S + RT + TMZ, S + PCV, S + RT, S + RT + PCV, S + TMZ, S + H-RT, and S. The 2-year overall survival ranking was S + RT + TMZ, S + H-RT + TMZ, S + RT, S + RT + PCV, S + H-RT, and S. The incidence of adverse events (≥3) was ranked from highest to lowest as follows: S + RT + PCV, S + RT + TMZ, S + PCV, S + H-RT, S + TMZ, and S + RT. In the isocitrate dehydrogenase 1/2 mutation nonchromosome 1p and 19q chromosome whole arm codeletion (IDHmt/noncoder) group, the S + RT + PCV and S + H-RT regimens had better 5-year PFS and 5-year OS. In the isocitrate dehydrogenase 1/2 mutation and chromosome 1p and 19q chromosome whole arm codeletion (IDHmt/coder) group, the 5-year PFS of each treatment regimen ranked from the best to the worst was S + RT + TMZ, S + RT + PCV, S + H-RT, S + RT, S + TMZ, and S. The order of 5-year OS from the best to the worst was S + H-RT, S + RT + TMZ, S + RT + PCV, S + RT, and S. In the isocitrate dehydrogenase 1/2 wild-type (IDHwt) group, the S + H-RT and S + TMZ regimens had better 5-year PFS.
CONCLUSIONS
This study revealed that both the S + RT + TMZ and S + RT + PCV regimens might be effective therapies for treating patients with low-grade gliomas. Among these, the S + RT + TMZ regimen seemed to be safer but might lead to tumor deterioration. In the IDHmt/coder type, the S + RT + TMZ scheme might have a significant advantage. In the IDHmt/noncoder type, the S + RT + PCV scheme might be more dominant, while in the IDHwt type, the S + H-RT and S + TMZ schemes also might be good treatment options.
Topics: Humans; Brain Neoplasms; Network Meta-Analysis; Isocitrate Dehydrogenase; Chemotherapy, Adjuvant; Glioma; Temozolomide
PubMed: 37673325
DOI: 10.1016/j.wneu.2023.08.125 -
JCO Oncology Practice Oct 2023To evaluate the use of interim positron emission tomography-computed tomography (PET-CT) scans and Deauville 5-point scale (5PS) score reporting for stage III/IV classic... (Observational Study)
Observational Study
Real-World Use of Positron Emission Tomography-Computed Tomography and Reported Deauville Scores in Advanced-Stage Classic Hodgkin Lymphoma: A Community Oncology Practice Perspective.
PURPOSE
To evaluate the use of interim positron emission tomography-computed tomography (PET-CT) scans and Deauville 5-point scale (5PS) score reporting for stage III/IV classic Hodgkin lymphoma (cHL) treated frontline (1L) in community oncology settings.
METHODS
This retrospective, observational study included adults with stage III/IV cHL initiating 1L doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine, or an escalated dosing regimen of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone within the US Oncology Network between January 2017 and October 2019. Data were collected from electronic health records and chart reviews and summarized descriptively.
RESULTS
A total of 262 patients were included; 48.9% were age 39 years or younger. Most were male (57%), White (59%), had an International Prognostic Score <4 (76%), and received 1L ABVD (74%). Forty-nine percent of patients had stage III and 51% had stage IV cHL. Of 258 patients with ≥1 PET-CT scan, 71% (n = 184) had an interim scan and 64% received ≥1 scan at an off-site location. Of patients treated 1L with ABVD who received a baseline and interim scan, Deauville 5PS scores were not documented for 45% of patients; in 90% of these cases, a standardized uptake value (SUV) was reported.
CONCLUSION
In community oncology settings, under-reporting of Deauville 5PS scores for interim PET-CT scans was observed. In the absence of Deauville 5PS scores, SUV results were generally provided. These results highlight educational opportunities that exist for PET-adapted ABVD, including consistency in reporting/utilization of Deauville 5PS scores to de-escalate or escalate treatment.
Topics: Adult; Humans; Male; Female; Hodgkin Disease; Positron Emission Tomography Computed Tomography; Vinblastine; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; Bleomycin; Doxorubicin; Dacarbazine; Positron-Emission Tomography
PubMed: 37651672
DOI: 10.1200/OP.23.00021 -
BMC Cancer Aug 2023Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is... (Randomized Controlled Trial)
Randomized Controlled Trial
Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly primary CNS lymphoma patients - the randomized phase III PRIMA-CNS trial.
BACKGROUND
Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed.
METHODS
This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-MTX (R-MTX) cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT.
DISCUSSION
The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach.
TRIAL REGISTRATION
German clinical trials registry DRKS00024085 registered March 29, 2023.
Topics: Aged; Humans; Quality of Life; Hematopoietic Stem Cell Transplantation; Procarbazine; Rituximab; Transplantation, Autologous; Lymphoma
PubMed: 37596517
DOI: 10.1186/s12885-023-11193-7