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Acta Clinica Croatica Feb 2022Treatment of glioblastoma is challenging due to its aggressive and highly invasive nature, and no significant advances in survival have been achieved recently. The aim...
Treatment of glioblastoma is challenging due to its aggressive and highly invasive nature, and no significant advances in survival have been achieved recently. The aim of our retrospective study was identification of predictive factors and consequent survival outcome in patients who underwent surgical and oncologic treatment of glioblastoma. The study was conducted at the Department of Neurosurgery, Osijek University Hospital Centre. The authors designed a retrospective cohort study in 63 patients who underwent surgical and oncologic treatment between January 1, 2012 and December 31, 2017. Data were collected by reviewing medical records of the patients with histologically proven glioblastoma. Statistical analysis of study results revealed a significant impact of postoperative radiotherapy (p=0.002) and chemotherapy (p=0.016) on progression-free survival and overall survival (p=0.001 and p=0.009, respectively). Postoperative Karnofsky performance scale (p=0.027) was found to be significant in progression-free survival, and so was the interval between surgery and commencement of oncologic therapy (p=0.049). In conclusion, overall survival and prognosis in the treatment of glioblastoma remain poor, although prompt approach in postoperative adjuvant treatments improved progression-free survival.
Topics: Brain Neoplasms; Glioblastoma; Humans; Neurosurgical Procedures; Prognosis; Retrospective Studies
PubMed: 35282478
DOI: 10.20471/acc.2021.60.03.06 -
Oncology Letters Apr 2022Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose...
Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose reduction or discontinuation in patients with recurrent glioma. The current study evaluated the safety and efficacy of modified procarbazine and lomustine (PC) chemotherapy that omits vincristine and reduces the lomustine dose compared with those of conventional PCV chemotherapy. Using electronic medical records, all patients with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary's Hospital or St. Vincent's Hospital were examined retrospectively. A total of 59 patients met the eligibility criteria. Among them, 15 patients received modified PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). The PC group presented a significantly lower hematology toxicity (anemia, 6.7 vs. 45.5%, P=0.02; thrombocytopenia 20.0 vs. 70.4%, P<0.001). Additionally, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s) or total cessation of chemotherapy, were significantly less frequent compared with the PCV group (26.7 vs. 68.2%, P=0.012). The overall survival of the PC group was also significantly longer than that of PCV group (396 vs. 232 days, P=0.042), while there was no significant difference in progression-free survival between the two groups (284.5 vs. 131 days, P=0.077). The results suggested that modified PC chemotherapy may be an alternative chemotherapeutic regimen with tolerable toxicity and without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are required to validate our findings.
PubMed: 35251345
DOI: 10.3892/ol.2022.13234 -
Cancers Jan 2022Nowadays, Hodgkin lymphoma (HL) has become highly curable. The young age at diagnosis and long life expectancy emphasize the importance of preventing long-term treatment...
Nowadays, Hodgkin lymphoma (HL) has become highly curable. The young age at diagnosis and long life expectancy emphasize the importance of preventing long-term treatment side effects, including bone mineral density (BMD) loss, in these patients. We aimed to evaluate the effects of first-line therapeutic modalities on BMD dynamics in HL patients, intending to identify individuals at risk for osteopenia. Demographics, HL risk factors, treatment, including cumulative steroid doses, and BMD of 213 newly-diagnosed HL patients (median age 29 years), treated at Rambam between 2008-2016, were analyzed. The main chemotherapy regimens applied were: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (EB; bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, prednisone). BMD was measured using PET/CT scans. BMD loss >15% was revealed in 48% of patients at therapy completion, with osteopenia prevalence of 4% and 14% at baseline and post-therapy, respectively. Cumulative hydrocortisone equivalent doses >3400 mg/m correlated with significant BMD reduction. Multivariate analysis at 6 months post-therapy identified age ≥30 years and EB-regimens as significant risk factors for BMD decrease >15%. Therapy-related BMD loss is common in HL patients. Its persistence is associated with age ≥30 years and EB treatment. Reduction of cumulative steroid doses and switch to non-gonadotoxic drugs should be considered.
PubMed: 35158763
DOI: 10.3390/cancers14030495 -
Annals of Lymphoma Sep 2021To provide a summary and analysis of the evidence for various agents applied as maintenance therapy and highlight ongoing trials or trials in development that evaluate...
OBJECTIVE
To provide a summary and analysis of the evidence for various agents applied as maintenance therapy and highlight ongoing trials or trials in development that evaluate the efficacy of maintenance therapy strategies in older patients with primary central nervous system lymphoma (PCNSL).
BACKGROUND
PCNSL are rare neoplasms that can have an aggressive course with short-lived remissions when compared to systemic diffuse large B-cell lymphoma (DLBCL). There is currently a paucity of evidence on treatment in older adults with PCNSL, who may be unfit to tolerate effective therapies for PCNSL. Those who can tolerate these therapies and survive PCNSL are at increased risk from developing treatment-related toxicity, functional decline, and debilitating neurotoxicity. While there is no clearly defined role for maintenance therapy after treatment of systemic DLBCL, it should be considered in PCNSL because central nervous system (CNS) recurrence often has a devastating and irreversible impact on neurologic function. Therefore, at least theoretically, use of effective maintenance therapy in older adults with PCNSL, either in lieu of consolidation or after consolidation therapy, may be better tolerated and help delay tumor progression, resulting in an improved overall global neurologic function and quality of life.
METHODS
We systematically searched MEDLINE (via PubMed) for all studies of drug treatments for maintenance therapy in PCNSL and also relied on expert opinion. We provide a summary and analysis of the evidence for various maintenance therapy agents, including methotrexate, rituximab, lenalidomide, temozolomide, ibrutinib, and procarbazine. We also highlight ongoing trials or trials in development that evaluate the efficacy of maintenance therapy in PCNSL.
CONCLUSIONS
Prospective clinical studies focusing on PCNSL patients who are not candidates for intensive post-induction therapy are scarce. To date, there are no studies that clarify whether maintenance therapy can be used in lieu of consolidation therapy with autologous stem cell transplant or radiation. Prospective studies may provide critical data regarding the identification of optimal agents, whether consolidation therapy could be replaced by maintenance therapy, and the overall role of maintenance therapy as a means to potentially improve survival and preserve quality of life and function in a vulnerable, older patient population.
PubMed: 35106521
DOI: 10.21037/aol-20-43 -
Journal of Clinical Oncology : Official... Apr 2022The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results.
METHODS
Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment.
RESULTS
In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively.
CONCLUSION
The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Follow-Up Studies; Hodgkin Disease; Humans; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Positron-Emission Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine; Young Adult
PubMed: 34990281
DOI: 10.1200/JCO.21.01777 -
Current Oncology (Toronto, Ont.) Nov 2021The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system...
The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol's PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m and vincristine 1.4 mg/m/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3-4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6-150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6-118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2-141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Clinical Trial Protocols as Topic; Humans; Lymphoma; Retrospective Studies
PubMed: 34898570
DOI: 10.3390/curroncol28060393 -
The Lancet. Oncology Jan 2022Children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma achieve an event-free survival at 5 years of about 90% after treatment... (Comparative Study)
Comparative Study Randomized Controlled Trial
Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised...
BACKGROUND
Children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma achieve an event-free survival at 5 years of about 90% after treatment with vincristine, etoposide, prednisone, and doxorubicin (OEPA) followed by cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) and radiotherapy, but long-term treatment effects affect survival and quality of life. We aimed to investigate whether radiotherapy can be omitted in patients with morphological and metabolic adequate response to OEPA and whether modified consolidation chemotherapy reduces gonadotoxicity.
METHODS
Our study was designed as a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial, and was carried out at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed intermediate-stage (treatment group 2) and advanced-stage (treatment group 3) classical Hodgkin lymphoma who were younger than 18 years and stratified according to risk using Ann Arbor disease stages IIAE, IIB, IIBE, IIIA, IIIAE, IIIB, IIIBE, and all stages IV (A, B, AE, and BE) were included in the study. Patients with early disease (treatment group 1) were excluded from this analysis. All patients were treated with two cycles of OEPA (1·5 mg/m vincristine taken intravenously capped at 2 mg, on days 1, 8, and 15; 125 mg/m etoposide taken intravenously on days 1-5; 60 mg/m prednisone taken orally on days 1-15; and 40 mg/m doxorubicin taken intravenously on days 1 and 15). Patients were randomly assigned to two (treatment group 2) or four (treatment group 3) cycles of COPP (500 mg/m cyclophosphamide taken intravenously on days 1 and 8; 1·5 mg/m vincristine taken intravenously capped at 2 mg, on days 1 and 8; 40 mg/m prednisone taken orally on days 1 to 15; and 100 mg/m procarbazine taken orally on days 1 to 15) or COPDAC, which was identical to COPP except that 250 mg/m dacarbazine administered intravenously on days 1 to 3 replaced procarbazine. The method of randomisation (1:1) was minimisation with stochastic component and was centrally stratified by treatment group, country, trial sites, and sex. The primary endpoint was event-free survival, defined as time from treatment start until the first of the following events: death from any cause, progression or relapse of classical Hodgkin lymphoma, or occurrence of secondary malignancy. The primary objectives were maintaining 90% event-free survival at 5 years in patients with adequate response to OEPA treated without radiotherapy and to exclude a decrease of 8% in event-free survival at 5 years in the embedded COPDAC versus COPP randomisation to show non-inferiority of COPDAC. Efficacy analyses are reported per protocol and safety in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (trial number NCT00433459) and EUDRACT (trial number 2006-000995-33), and is closed to recruitment.
FINDINGS
Between Jan 31, 2007, and Jan 30, 2013, 2102 patients were recruited. 737 (35%) of the 2102 recruited patients were in treatment group 1 (early-stage disease) and were not included in our analysis. 1365 (65%) of the 2102 patients were in treatment group 2 (intermediate-stage disease; n=455) and treatment group 3 (advanced-stage disease; n=910). Of these 1365, 1287 (94%) patients (435 [34%] of 1287 in treatment group 2 and 852 [66%] of 1287 in treatment group 3) were included in the titration trial per-protocol analysis. 937 (69%) of 1365 patients were randomly assigned to COPP (n=471) or COPDAC (n=466) in the embedded trial. Median follow-up was 66·5 months (IQR 62·7-71·7). Of 1287 patients in the per-protocol group, 514 (40%) had an adequate response to treatment and were not treated with radiotherapy (215 [49%] of 435 in treatment group 2 and 299 [35%] of 852 in treatment group 3). 773 (60%) of 1287 patients with inadequate response were scheduled for radiotherapy (220 [51%] of 435 in the treatment group 2 and 553 [65%] of 852 in treatment group 3. In patients who responded adequately, event-free survival rates at 5 years were 90·1% (95% CI 87·5-92·7). event-free survival rates at 5 years in 892 patients who were randomly assigned to treatment and analysed per protocol were 89·9% (95% CI 87·1-92·8) for COPP (n=444) versus 86·1% (82·9-89·4) for COPDAC (n=448). The COPDAC minus COPP difference in event-free survival at 5 years was -3·7% (-8·0 to 0·6). The most common grade 3-4 adverse events (intention-to-treat population) were decreased haemoglobin (205 [15%] of 1365 patients during OEPA vs 37 [7%] of 528 treated with COPP vs 20 [2%] of 819 treated with COPDAC), decreased white blood cells (815 [60%] vs 231 [44%] vs 84 [10%]), and decreased neutrophils (1160 [85%] vs 223 [42%] vs 174 [21%]). One patient in treatment group 2 died of sepsis after the first cycle of OEPA; no other treatment-related deaths occurred.
INTERPRETATION
Our results show that radiotherapy can be omitted in patients who adequately respond to treatment, when consolidated with COPP or COPDAC. COPDAC might be less effective, but is substantially less gonadotoxic than COPP. A high proportion of patients could therefore be spared radiotherapy, eventually reducing the late effects of treatment. With more refined criteria for response assessment, the number of patients who receive radiotherapy will be further decreased.
FUNDING
Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder Gießen, Kinderkrebsstiftung Mainz, Tour der Hoffnung, Menschen für Kinder, Programme Hospitalier de Recherche Clinique, and Cancer Research UK.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Female; Follicle Stimulating Hormone; Hodgkin Disease; Humans; Male; Neoplasm Staging; Prednisone; Procarbazine; Vincristine
PubMed: 34895479
DOI: 10.1016/S1470-2045(21)00470-8 -
Frontiers in Pharmacology 2021Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic... (Review)
Review
Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic regimens. Nevertheless, some treatments were accompanied with toxicities. In the current study, a network meta-analysis (NMA) was conducted to compare the efficacies and toxicities of different chemotherapy regimens for advanced Hodgkin lymphoma (HL). We reviewed PubMed and EMBASE databases from inception to May 2018, and identified randomized controlled trials (RCTs) in which advanced HL patients received chemotherapy. Fourteen eligible RCTs published between 1992 and 2017 were enrolled in this NMA. These studies included a total of 5,964 HL patients, and assessed at least one of seven different chemotherapy regimens. Direct and indirect evidence was combined to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), and to establish a surface under the cumulative ranking (SUCRA) curve. A cluster analysis was performed to evaluate efficacies and toxicities of different regimens. The COPP + ABVD (cyclophosphamide + vincristine + procarbazine + prednisone + doxorubicin + bleomycin + vinblastine + dacarbazine) regimen had the highest SUCRA partial response and overall remission rate values, while the ABVD regimen resulted in the lowest incidences of anemia, thrombocytopenia, neutropenia, and leucopenia. Cluster analysis revealed that COPP + ABVD had the best efficacy against advanced HL among the seven regimens, and ABVD had the lowest toxicity.
PubMed: 34867316
DOI: 10.3389/fphar.2021.694545 -
Frontiers in Immunology 2021DNA methylation patterns are essential in understanding carcinogenesis. However, the relationship between DNA methylation and the immune process has not been clearly...
DNA methylation patterns are essential in understanding carcinogenesis. However, the relationship between DNA methylation and the immune process has not been clearly established-this study aimed at elucidating the interaction between glioma and DNA methylation, consolidating glioma classification and prognosis. A total of 2,483 immune-related genes and 24,556 corresponding immune-related methylation probes were identified. From the Cancer Genome Atlas (TCGA) glioma cohort, a total of 683 methylation samples were stratified into two different clusters using unsupervised clustering, and eight types of other cancer samples from the TCGA database were shown to exhibit excellent distributions. A total of 3,562 differentially methylated probes (DMPs) were selected and used for machine learning. A five-probe signature was established to evaluate the prognosis of glioma as well as the potential benefits of radiotherapy and Procarbazine, CCNU, Vincristine (PCV) treatment. Other prognostic clinical models, such as nomogram and decision tree, were also evaluated. Our findings confirmed the interactions between immune-related methylation patterns and glioma. This novel approach for cancer molecular characterization and prognosis should be validated in further studies.
Topics: Aged; Brain Neoplasms; Clinical Decision-Making; DNA Methylation; Databases, Genetic; Decision Trees; Epigenome; Epigenomics; Female; Glioma; Humans; Machine Learning; Male; Middle Aged; Nomograms; Precision Medicine; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Tumor Microenvironment
PubMed: 34804019
DOI: 10.3389/fimmu.2021.737650 -
Blood Research Dec 2021High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly...
R-MPV followed by high-dose chemotherapy with thiotepa-based and autologous stem cell transplantation for newly diagnosed primary central nervous system lymphoma: a single-center experience.
BACKGROUND
High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL).
METHODS
In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa- based conditioning regimen but did not undergo radiotherapy.
RESULTS
The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions. Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis.
CONCLUSION
The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.
PubMed: 34801986
DOI: 10.5045/br.2021.2021073