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Journal of Clinical Oncology : Official... Feb 2023Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy...
PURPOSE
Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease.
METHODS
Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation.
RESULTS
Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided = .04).
CONCLUSION
Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.
Topics: Humans; Female; Adult; Male; Hodgkin Disease; Vinblastine; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Bleomycin; Dacarbazine; Neoplasm Staging; Positron-Emission Tomography; Vincristine; Prednisone
PubMed: 36269899
DOI: 10.1200/JCO.22.00947 -
Clinical Nuclear Medicine Jan 2024We 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...
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.
Topics: Adult; Humans; Adolescent; Hodgkin Disease; Prognosis; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Antineoplastic Combined Chemotherapy Protocols; Tumor Burden; Retrospective Studies; Doxorubicin; Bleomycin; Dacarbazine; Vinblastine
PubMed: 38015041
DOI: 10.1097/RLU.0000000000004930 -
Critical Reviews in Oncology/hematology Apr 2020Advanced classical Hodgkin lymphoma (cHL) is a rare lymphoid disease characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells. Each year, cHL accounts for... (Review)
Review
Advanced classical Hodgkin lymphoma (cHL) is a rare lymphoid disease characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells. Each year, cHL accounts for 0.5% of all new cancer diagnoses and about 80% are diagnosed with advanced stage disease. Given the significant improvement in cure rates, the focus of treatment has shifted towards minimization of acute and long-term toxicities. PET-adapted strategies have largely been adopted as standard of care in the United States in an attempt to balance toxicities with adequate lymphoma control. However, the appropriate upfront chemotherapy regimen (ABVD versus eBEACOPP) remains controversial.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Neoplasm Staging; Positron-Emission Tomography; Predictive Value of Tests; Prednisone; Procarbazine; Treatment Outcome; Vinblastine; Vincristine
PubMed: 32109715
DOI: 10.1016/j.critrevonc.2020.102897 -
Veterinary and Comparative Oncology Sep 2023Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP...
Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance. The objective of this study was to report the clinical outcomes and toxicity of 36 dogs with relapsed or refractory multicentric lymphoma treated with a modified MOPP protocol whereby vincristine was replaced with vinblastine (MVPP). The overall response rate to MVPP was 25% with a median progression free survival of 15 days and a median overall survival of 45 days. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses.
Topics: Animals; Dogs; Prednisone; Vinblastine; Mechlorethamine; Vincristine; Procarbazine; Neoplasm Recurrence, Local; Dog Diseases; Lymphoma; Antineoplastic Combined Chemotherapy Protocols; Lymphoma, Non-Hodgkin; Doxorubicin
PubMed: 37222086
DOI: 10.1111/vco.12913 -
British Journal of Haematology Aug 2023Management of classical Hodgkin lymphoma in older patients is challenging due to poor tolerance of the chemotherapy regimens used in younger patients. We modified the...
Management of classical Hodgkin lymphoma in older patients is challenging due to poor tolerance of the chemotherapy regimens used in younger patients. We modified the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone), whereby bleomycin and etoposide were removed and cyclophosphamide dose was reduced, for older patients with co-morbidities. Here we present data from the first 41 patients treated with 'ACOPP' across 3 centres, demonstrating that it can be delivered, with a favourable toxicity profile (TRM 2%) and promising efficacy (2-year PFS and OS, 73% (95% CI: 52-94) and 93% (95% CI: 80-100) respectively).
Topics: Humans; Aged; Hodgkin Disease; Vincristine; Retrospective Studies; Procarbazine; Etoposide; Cyclophosphamide; Doxorubicin; Bleomycin; Antineoplastic Combined Chemotherapy Protocols; Prednisone
PubMed: 37357380
DOI: 10.1111/bjh.18947 -
No Shinkei Geka. Neurological Surgery Jan 2022Primary central nervous system lymphoma(PCNSL)is an aggressive, extranodal non-Hodgkin lymphoma that arises from the central nervous system, eyes, leptomeninges, and the...
Primary central nervous system lymphoma(PCNSL)is an aggressive, extranodal non-Hodgkin lymphoma that arises from the central nervous system, eyes, leptomeninges, and the spinal cord. Most PCNSLs are a type of diffuse large B-cell lymphoma(DLBCL), and the majority are categorized as a non-germinal center B-cell(GCB)subtype. Recent genetic studies have revealed several common genetic abnormalities in PCNSL, such as and mutations, suggesting dependence on the B-cell receptor/Toll-like receptor signaling pathway. These genetic findings have rationalized targeted therapy targeting Bruton's tyrosine kinase(BTK), a key molecule of the B-cell receptor pathway in PCNSL and systemic non-GCB DLBCL. The first-generation BTK inhibitor ibrutinib has been widely studied in clinical trials for PCNSL and systemic non-GCB DLBCL. In Japan, a second-generation BTK inhibitor tirabrutinib was studied in a phase I/II trial and approved by the Japanese Ministry of Health and Welfare in March 2020 for relapsed and refractory PCNSL. While the current standard-of-care therapy for PCNSL is methotrexate(MTX)-based multi-agent induction immunochemotherapy like R-MPV(rituximab, MTX, procarbazine, and vincristine)followed by consolidation chemotherapy and/or radiation therapy, further investigation into the optimal use of BTK inhibitors in the standard-of-care therapy of PCNSL is warranted.
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Precision Medicine
PubMed: 35169086
DOI: 10.11477/mf.1436204531 -
Haematologica Nov 2023Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programmes developed for the...
Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programmes developed for the general population, and the utility of these programmes has not been tested in HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings. HL survivors treated ≥5 years ago with mustine/procarbazine and/or thoracic radiation, were identified from a follow-up database and invited to participate. Participants underwent a low-dose CT (LDCT) reported using protocols validated for the general population. Two hundred and eighteen individuals were invited, 123 were eligible, 102 were screened (58% response rate): 58% female, median age 52 years, median 22 years since HL treatment. 91.4% were deemed to have made an informed decision; participation was not influenced by age, gender, years since treatment or deprivation. Only 3/35 ever-smokers met criteria for LCS through the programme aimed at the general population. Baseline LDCT results were: 90 (88.2%) negative, 10 (9.8%) indeterminate, 2 (2.0%) positive. Two 3-month surveillance scans were positive. Of 4 positive scans, 2 patients were diagnosed with small-cell lung cancer; 1 underwent curative surgery. Coronary artery calcification was detected in 36.3%, and clinically significant incidental findings in 2.9%. LDCT protocols validated in ever-smokers can detect asymptomatic early-stage lung cancers in HL survivors. This finding, together with screening uptake and low false positive rates, supports further research to implement LCS for HL survivors.
PubMed: 37981893
DOI: 10.3324/haematol.2023.283287 -
JCO Global Oncology Mar 2021Pediatric neuro-oncology resources are mostly unknown in Chile. We report the human and material resources available in Chilean hospitals providing pediatric...
PURPOSE
Pediatric neuro-oncology resources are mostly unknown in Chile. We report the human and material resources available in Chilean hospitals providing pediatric neuro-oncology services.
METHODS
A cross-sectional survey was distributed to 17 hospitals providing pediatric neuro-oncology services (Programa Infantil Nacional de Drogas Antineoplásicas [PINDA] hospitals, 11; private, 6).
RESULTS
Response rate was 71% (PINDA, 8; private, 4). Pediatric neuro-oncology services were mainly provided within general hospitals (67%). Registries for pediatric CNS tumors and chemotherapy-related toxicities were available in 100% and 67% of hospitals, respectively. CNS tumors were treated by pediatric oncologists in 92% of hospitals; none were formally trained in neuro-oncology. The most used treatment protocols were the national PINDA protocols. All WHO essential medicines for childhood cancer were available in more than 80% of the hospitals except for gemcitabine, oxaliplatin, paclitaxel, and procarbazine. The median number of pediatric neurosurgeons per hospital was two (range, 2-6). General neuroradiologists were available in 83% of the centers. Pathology specimens were sent to neuropathologists (58%), adult pathologists (25%), and pediatric pathologists (17%). Intensity-modulated radiotherapy, conformal radiotherapy, and cobalt radiotherapy were used by 67%, 58%, and 42% of hospitals, respectively. Only one private hospital performed autologous hematopoietic cell transplant for children with CNS tumors.
CONCLUSION
A wide range of up-to-date treatment modalities are available for children with CNS tumors. Our survey highlights future directions to improve the pediatric neuro-oncology services available in Chile such as the expansion of multidisciplinary clinics, palliative care services, long-term cancer survivorship programs, dedicated clinical research support teams, establishing standardized mechanism for sending pathologic specimen for second opinion to international specialized centers, and establishing specialized neuro-oncology training program.
Topics: Central Nervous System Neoplasms; Child; Chile; Cross-Sectional Studies; Hematopoietic Stem Cell Transplantation; Humans; Medical Oncology
PubMed: 33788596
DOI: 10.1200/GO.20.00430 -
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 -
EJHaem Nov 2022PEP-C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed...
PEP-C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed refractory lymphoma. To our knowledge, no data on PEP-C have been reported since the original group described the regimen. Here we present a multicentre retrospective cohort reporting our use of PEP-C in 92 patients over an 8-year period. We find that even heavily pretreated lymphoma can respond to PEP-C, particularly low-grade lymphoma (including mantle cell) and lymphoma that was sensitive to the previous line of systemic therapy (chemosensitive). These characteristics may help in the selection of patients likely to derive benefit. The median overall survival of patients with chemosensitive lymphoma treated with PEP-C is 217 days. Within the limitations of a retrospective cohort, we find that PEP-C is well tolerated: the most common toxicity leading to discontinuation is marrow suppression. We suggest that PEP-C should be considered for patients with relapsed refractory lymphoma in two settings: first, where there is no licensed alternative; and second, where the licensed alternative is an intravenous drug and the patient would prefer to choose an oral chemotherapy option.
PubMed: 36467809
DOI: 10.1002/jha2.537