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ACS Applied Bio Materials Jul 2021Imaging hydrogel-based local drug delivery to the brain after tumor resection has implications for refining treatments, especially for brain tumors with poor prognosis...
Imaging hydrogel-based local drug delivery to the brain after tumor resection has implications for refining treatments, especially for brain tumors with poor prognosis and high recurrence rate. Here, we developed a series of self-healing chitosan-dextran (CD)-based hydrogels for drug delivery to the brain. These hydrogels are injectable, self-healing, mechanically compatible, and detectable by chemical exchange saturation transfer magnetic resonance imaging (CEST MRI). CD hydrogels have an inherent CEST contrast at 1.1 ppm, which decreases as the stiffness increases. We further examined the rheological properties and CEST contrast of various chemotherapeutic-loaded CD hydrogels, including gemcitabine (Gem), doxorubicin, and procarbazine. Among these formulations, Gem presented the best compatibility with the rheological (': 215.3 ± 4.5 Pa) and CEST properties of CD hydrogels. More importantly, the Gem-loaded CD hydrogel generated another CEST readout at 2.2 ppm (11.6 ± 0.1%) for monitoring Gem. This enabled independent and simultaneous imaging of the drug and hydrogel integrity using a clinically relevant 3 T MRI scanner. In addition, the Gem-loaded CD hydrogel exhibited a longitudinal antitumor efficacy of Gem over a week . Furthermore, the CD hydrogel could be visualized by CEST after brain injection with a contrast of 7.38 ± 2.31%. These natural labels on both the chemotherapeutics and hydrogels demonstrate unique image-guided local drug delivery for brain applications.
Topics: Chitosan; Doxorubicin; Drug Delivery Systems; Hydrogels; Magnetic Resonance Imaging
PubMed: 35006724
DOI: 10.1021/acsabm.1c00411 -
Neurology Aug 2023Primary CNS lymphoma (PCNSL), a rare CNS malignancy, is usually treated with high-dose methotrexate in the first-line setting, typically followed by consolidation...
BACKGROUND AND OBJECTIVES
Primary CNS lymphoma (PCNSL), a rare CNS malignancy, is usually treated with high-dose methotrexate in the first-line setting, typically followed by consolidation therapy. Due to the broad range of currently available treatments for PCNSL, comparability in long-term follow-up studies is limited, and data are scattered across small studies.
METHODS
In this study, we report the long-term survival of patients with newly diagnosed immunocompetent PCNSL, enrolled in a phase II trial from June 2005 to September 2011. Patients were treated using rituximab, methotrexate, vincristine, and procarbazine (R-MVP) chemotherapy followed by high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) in those with partial or complete response to R-MVP. In a post hoc analysis, clinical and imaging features were evaluated in those still alive.
RESULTS
26 of 32 patients underwent HDC-ASCT consolidation. Of them, 3 patients died of treatment-related toxicity and 2 due to disease progression within 1 year of ASCT. None of the remaining 21 patients had disease progression with a median follow-up of 12.1 years and were included in the analysis. Compared with the post-HDC-ASCT assessment, at the last follow-up, there was no significant difference in the median Karnofsky Performance Status (80 [range: 60-100] vs 90 [range: 70-100]), the median Neurologic Assessment in Neuro-Oncology score (1 [range: 0-4] vs 1 [range: 0-5]), and leukoencephalopathy score (1 [range: 0-3] vs 1 [range: 1-4]).
DISCUSSION
Long-term follow-up demonstrated that treatment was well tolerated in most patients enrolled in this study, with stable leukoencephalopathy on imaging and stable clinical performance status. Disease recurrence was not observed beyond 2 years after HDC-ASCT consolidation.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Combined Modality Therapy; Disease Progression; Hematopoietic Stem Cell Transplantation; Leukoencephalopathies; Lymphoma; Methotrexate; Neoplasm Recurrence, Local; Rituximab; Transplantation, Autologous; Vincristine
PubMed: 37344228
DOI: 10.1212/WNL.0000000000207490 -
BMC Cancer Feb 2021Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV...
BACKGROUND
Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice.
METHODS
We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities.
RESULTS
Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia.
CONCLUSION
Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Glioma; Humans; Incidence; Ireland; Lomustine; Male; Neoplasm Grading; Procarbazine; Retrospective Studies; Time Factors; Vincristine
PubMed: 33557783
DOI: 10.1186/s12885-021-07809-5 -
Frontiers in Veterinary Science 2024Canine gastrointestinal (GI) and hepatosplenic (HS) high-grade (large cell) lymphomas are uncommon forms of canine lymphomas, with a very poor response to chemotherapy...
Canine gastrointestinal (GI) and hepatosplenic (HS) high-grade (large cell) lymphomas are uncommon forms of canine lymphomas, with a very poor response to chemotherapy and a very poor prognosis. Currently, there are no established effective chemotherapy protocols for canine GI/HS lymphomas. This case series aimed to retrospectively evaluate the efficacy of lomustine-based protocols L-LOP (L-asparaginase, lomustine, vincristine, and prednisolone) and L-LOPP (with the addition of procarbazine) for treatment of canine GI/HS lymphomas. Medical records of dogs with cytologically or histologically diagnosed lymphoma at CityU Veterinary Medical Centre from 2019 to 2022 were retrospectively reviewed. The L-LOP/LOPP treatment protocol was well tolerated with rare severe adverse events. Median progression-free survival for GI and HS lymphoma was 56 days (range, 10-274 days) and 57 days (range 8-135 days) respectively; while median survival time for GI and HS lymphoma was 93 days (range 10-325 days) and 210 days (range 8-240 days) respectively.
PubMed: 38846784
DOI: 10.3389/fvets.2024.1373180 -
Neuro-oncology Practice Feb 2021Advances in treatment of oligodendroglioma represent arguably the most significant recent development in the treatment of brain tumors, with multiple clinical trials... (Review)
Review
Advances in treatment of oligodendroglioma represent arguably the most significant recent development in the treatment of brain tumors, with multiple clinical trials demonstrating that median survival is approximately doubled in patients with World Health Organization grade II and III 1p/19q codeleted gliomas (ie, oligodendrogliomas) treated with procarbazine, lomustine, vincristine chemotherapy and radiation vs radiation alone. However, chemoradiotherapy itself is not without morbidity, including both short-term toxicities primarily related to chemotherapy and longer-term cognitive issues likely due to radiation. Patients and physicians both desire maximally effective therapy with minimal toxicity, and it remains unclear whether some patients with macroscopic residual disease after surgery can safely delay therapy, to avoid or delay toxicity, while simultaneously preserving the full benefits of treatment. In this article, experts in the field discuss the rationale for the approaches of up-front treatment with chemoradiotherapy and initial observation, respectively.
PubMed: 33664965
DOI: 10.1093/nop/npaa037 -
Australian Journal of General Practice Dec 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Dyspnea; Etoposide; Hematuria; Hepatomegaly; Hodgkin Disease; Humans; Lower Urinary Tract Symptoms; Lymphadenopathy; Male; Marfan Syndrome; Mediastinum; Neoplasm Staging; Pectus Carinatum; Pleural Effusion; Prednisone; Procarbazine; Splenomegaly; Tomography, X-Ray Computed; Vinblastine; Vincristine; Young Adult
PubMed: 31774988
DOI: 10.31128/AJGP-07-19-5019 -
Cureus Apr 2022Introduction Bleomycin is a major antimitotic agent in the first-line treatment for Hodgkin's lymphoma. The main limitation of its use is its pulmonary toxicity. The...
Introduction Bleomycin is a major antimitotic agent in the first-line treatment for Hodgkin's lymphoma. The main limitation of its use is its pulmonary toxicity. The objectives of this study are to find out the risk factors for the occurrence of bleomycin-induced lung toxicity in patients with Hodgkin's lymphoma and, on the other hand, to determine if positron emission tomography scan is a reliable means of early detection of this toxicity. Methods This is a retrospective study conducted in the clinical Hematology Department of Mohammed V Military Instruction Hospital, Rabat, Morocco. All patients with Hodgkin's lymphoma and treated with a bleomycin-based chemotherapy were included. The impact of different clinical and biological factors on the risk of bleomycin-induced lung toxicity occurrence was assessed using univariate and multivariate logistic regression. The benefit of positron emission tomography, usually performed as part of the re-assessment of Hodgkin's lymphoma after two and four cycles, has been evaluated in the detection of bleomycin-induced lung toxicity. Results Among 124 patients included in the study, 18 (14.5%) patients experienced bleomycin-induced lung toxicity. On multivariate analysis, smoking (p = 0.038) and the use of the ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) compared to the escalated BEACOPPe regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) (p = 0.018) were statistically significant risk factors. After two and four courses of therapy, the positron emission tomography was able to predict the occurrence of bleomycin-induced lung toxicity before the appearance of clinical symptoms only in 36.4 % and 12.5% of patients, respectively. Conclusion Studies to identify risk factors for the development of bleomycin-induced lung toxicity are crucial to reduce toxicity in the treatment of Hodgkin's lymphoma. However, two- and four-cycle positron emission tomography scans cannot be considered as a reliable means of early detection of this toxicity.
PubMed: 35419251
DOI: 10.7759/cureus.23993 -
Clinical and Translational Radiation... Jul 2023Oligodendrogliomas (ODG) are rare, diffusely infiltrating brain tumors, defined by their 1p/19q-codeletion and isocitrate dehydrogenase (IDH) mutation. Herein, we...
BACKGROUND
Oligodendrogliomas (ODG) are rare, diffusely infiltrating brain tumors, defined by their 1p/19q-codeletion and isocitrate dehydrogenase (IDH) mutation. Herein, we analyze the influence of various tumor and patient characteristics on progression-free survival (PFS) and overall survival (OS) in a homogeneous patient cohort.
MATERIAL AND METHODS
Patients treated for a 1p/19q-codeleted and IDH-mutant ODG were evaluated. The patient and tumor characteristics were analyzed for their influence on PFS and OS.
RESULTS
One-hundred-fourteen patients met the inclusion criteria. The median clinical and radiographic follow-up periods were 68.6 and 69.8 months. The median PFS and OS were 66.9 and 236.0 months, respectively. The 2-, 4- and 6-year PFS rates were 89.5%, 76.3%, and 46.0%. The 2-, 4- and 6-year OS rates were 99.0%, 97.9%, and 96.2%. For WHO grade 2 ODG, extent of resection ( 0.01, 0.01; 0.02, 0.02), radiotherapy ( 0.01, < 0.01) and chemotherapy ( 0.01, 0.01) were associated with a prolonged PFS. For WHO grade 3 ODG, only a combined radiochemotherapy (RCT) lowered the risk of progression in the multivariable analysis ( = 0.02, 0.09). Most RCT patients received temozolomide (TMZ) instead of procarbazine, lomustine, and vincristine.
CONCLUSION
Whereas previous studies often comprise tumors with IDH wild type status and without 1p/19q-codeletion, this homogeneous ODG cohort, as defined by the current WHO classification, demonstrated PFS benefits for various therapies, especially concerning RCT. While this is generally in accordance with comparable studies, more prospective work on homogeneous patient cohorts is required to refine treatment guidelines and to determine the role of TMZ in ODG.
PubMed: 37216045
DOI: 10.1016/j.ctro.2023.100626 -
Blood Aug 2023The optimal first-line treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) diagnosed in early stages is largely undefined. We, therefore, analyzed 100...
The optimal first-line treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) diagnosed in early stages is largely undefined. We, therefore, analyzed 100 NLPHL patients treated in the randomized HD16 (early-stage favorable; n = 85) and HD17 (early-stage unfavorable; n = 15) studies. These studies investigated the omission of consolidation radiotherapy (RT) in patients with a negative interim positron emission tomography (iPET) (ie, Deauville score <3) after chemotherapy (HD16: 2× doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]; HD17: 2× escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP] plus 2× ABVD). Patients with NLPHL treated in the HD16 and HD17 studies had 5-year progression-free survival (PFS) rates of 90.3% and 92.9%, respectively. Thus, the 5-year PFS did not differ significantly from that of patients with classical Hodgkin lymphoma treated within the same studies (HD16: P = .88; HD17: P = .50). Patients with early-stage favorable NLPHL who had a negative iPET after 2× ABVD and did not undergo consolidation RT tended to have a worse 5-year PFS than patients with a negative iPET who received consolidation RT (83% vs 100%; P = .05). There were 10 cases of NLPHL recurrence. However, no NLPHL patient died during follow-up. Hence, the 5-year overall survival rate was 100%. Taken together, contemporary Hodgkin lymphoma-directed treatment approaches result in excellent outcomes for patients with newly diagnosed early-stage NLPHL and, thus, represent valid treatment options. In early-stage favorable NLPHL, consolidation RT appears necessary after 2× ABVD to achieve the optimal disease control irrespective of the iPET result.
Topics: Humans; Hodgkin Disease; Bleomycin; Doxorubicin; Dacarbazine; Vinblastine; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Vincristine; Positron-Emission Tomography; Prednisone
PubMed: 37257195
DOI: 10.1182/blood.2023019939 -
The Oncologist May 2021IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine...
Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.
BACKGROUND
IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.
METHODS
In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.
RESULTS
The 4-year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38-0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41-0.97; p = .0348) in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30-1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001).
CONCLUSION
RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.
IMPLICATIONS FOR PRACTICE
In the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH-mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH-mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression-free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH-mutant AA.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Humans; Lomustine; Procarbazine; Retrospective Studies; Temozolomide; Vincristine
PubMed: 33524191
DOI: 10.1002/onco.13701