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Cureus Jun 2023Varicella zoster virus (VZV)-associated plexopathy mainly occurs in patients over 60 years old. Postherpetic neuralgia is a well-known complication of herpes zoster...
Varicella zoster virus (VZV)-associated plexopathy mainly occurs in patients over 60 years old. Postherpetic neuralgia is a well-known complication of herpes zoster (HZ); however, segmental zoster paresis secondary to HZ was reported in 1-20% of cases in the literature. Magnetic resonance imaging (MRI) findings may be positive in up to 70% of the patients. We describe a 43-year-old male patient with a history of grade two left frontal oligodendroglioma, which was treated with two partial resections, radiation treatment and procarbazine/lomustine, who presented with left upper extremity pain and developed a blistering rash in a dermatomal pattern in the left proximal upper extremity two weeks after the initial symptoms. He was diagnosed with shingles and treated with steroids and acyclovir with minimal improvement. Six weeks after the initial symptoms, a physical exam revealed left deltoid, supraspinatus and infraspinatus weakness with normal muscle stretch reflexes and decreased sensation on the C5 dermatome. Electromyography (EMG) revealed absent left lateral antebrachial cutaneous sensory nerve action potentials (SNAP) amplitude and a small left radial SNAP amplitude compared to the right side. Evidence of ongoing denervation with reinnervation was seen in the left upper trunk-supplied muscles. MRI of the brachial plexus was negative for any abnormalities. The patient was diagnosed with VZV-associated plexopathy, which improved with pregabalin and physical therapy. Our patient was significantly younger than expected in the HZ group. MRI usually shows T2 hyperintensities and thickening of the nerve roots in patients with VZV-associated plexopathy. However, the presentation, onset of symptoms, characteristics of the rash, and clinical course were diagnostic of HZ, and the weakness pattern, supported by the EMG findings, was diagnostic of VZV-associated plexopathy.
PubMed: 37404385
DOI: 10.7759/cureus.39876 -
Archives of Toxicology Aug 2023Mutagenicity testing is an essential component of health safety assessment. Duplex Sequencing (DS), an emerging high-accuracy DNA sequencing technology, may provide...
Mutagenicity testing is an essential component of health safety assessment. Duplex Sequencing (DS), an emerging high-accuracy DNA sequencing technology, may provide substantial advantages over conventional mutagenicity assays. DS could be used to eliminate reliance on standalone reporter assays and provide mechanistic information alongside mutation frequency (MF) data. However, the performance of DS must be thoroughly assessed before it can be routinely implemented for standard testing. We used DS to study spontaneous and procarbazine (PRC)-induced mutations in the bone marrow (BM) of MutaMouse males across a panel of 20 diverse genomic targets. Mice were exposed to 0, 6.25, 12.5, or 25 mg/kg-bw/day for 28 days by oral gavage and BM sampled 42 days post-exposure. Results were compared with those obtained using the conventional lacZ viral plaque assay on the same samples. DS detected significant increases in mutation frequencies and changes to mutation spectra at all PRC doses. Low intra-group variability within DS samples allowed for detection of increases at lower doses than the lacZ assay. While the lacZ assay initially yielded a higher fold-change in mutant frequency than DS, inclusion of clonal mutations in DS mutation frequencies reduced this discrepancy. Power analyses suggested that three animals per dose group and 500 million duplex base pairs per sample is sufficient to detect a 1.5-fold increase in mutations with > 80% power. Overall, we demonstrate several advantages of DS over classical mutagenicity assays and provide data to support efforts to identify optimal study designs for the application of DS as a regulatory test.
Topics: Male; Mice; Animals; Procarbazine; Mutation Rate; Bone Marrow; Mutagens; Mutation; Mutagenicity Tests; Mice, Transgenic; Lac Operon
PubMed: 37341741
DOI: 10.1007/s00204-023-03527-y -
Frontiers in Oncology 2023Peripheral T-cell lymphoma (PTCL) is a rare and heterogenous hematologic malignancy with poor prognosis especially in elderly and frail patients who are not eligible for...
PURPOSE
Peripheral T-cell lymphoma (PTCL) is a rare and heterogenous hematologic malignancy with poor prognosis especially in elderly and frail patients who are not eligible for intensive treatment. The resulting palliative setting necessitates tolerable but effective schedules for outpatient treatment. TEPIP is a locally developed, all-oral low-dose regimen comprising trofosfamide, etoposide, procarbazine, idarubicin, and prednisolone.
METHODS
In this observational retrospective, single-center study, the safety and efficacy of TEPIP was evaluated in 12 patients (pts.) with PTCL treated at the University Medical Center Regensburg between 2010 and 2022. The endpoints were overall response rate (ORR) and overall survival (OS), and adverse events were individually reported according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria.
RESULTS
The enrolled cohort was characterized by advanced age (median 70 years), extensive disease (100% Ann Arbor ≥stage 3), and poor prognosis (75% high/high-intermediate international prognostic index). The most common subtype was angioimmunoblastic T-cell lymphoma (8/12), and 11/12 patients had relapsed or refractory disease at TEPIP onset with a median of 1.5 prior treatment regimens. After a median of 2.5 TEPIP cycles (total of 83 cycles), the ORR was 42% (complete remission 25%), and the OS reached a median of 185 days. Any grade of adverse event (AE) occurred in 8/12 patients, with four patients showing AE ≥CTCAE grade 3 (33%), and the AEs were mainly non-hematological.
CONCLUSION
TEPIP demonstrated competitive efficacy with a tolerable safety profile in a highly palliative cohort of patients with difficult-to-treat PTCL. The all-oral application, which makes outpatient treatment possible, is particularly noteworthy.
PubMed: 37305564
DOI: 10.3389/fonc.2023.1177330 -
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 -
Cureus Mar 2023Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma, which uncommonly presents with optic nerve infiltration (ONI). ONI has been...
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma, which uncommonly presents with optic nerve infiltration (ONI). ONI has been reported mostly in relapse cases of PCNSL and is rarely the sole manifestation of the disease at the time of diagnosis. We report a case of a 69-year-old female who presented with progressive visual impairment with relative afferent pupillary defect (RAPD) on examination. Orbital and cranial magnetic resonance imaging (MRI) revealed bilateral optic nerve sheath contrast enhancement with an incidental finding of a right frontal lobe mass. Routine cerebrospinal fluid analysis and cytology were unremarkable. Excision biopsy of the frontal lobe mass yielded the diagnosis of a diffuse B-cell lymphoma. Intraocular lymphoma was excluded on ophthalmologic workup. Whole body positron emission tomography scan did not reveal extracranial involvement establishing the diagnosis of PCNSL. Chemotherapy was initiated with rituximab, methotrexate, procarbazine, and vincristine as induction regimen and cytarabine as consolidation therapy. On follow-up, the visual acuity of both eyes significantly improved with the resolution of RAPD. Repeat cranial MRI did not show a recurrence of the lymphomatous process. To the best of the authors' knowledge, ONI as the initial presentation at the time of PCNSL diagnosis has only been reported three times. The present case's unusual presentation highlights the need to consider PCNSL as a differential diagnosis in patients who present with visual deterioration and optic nerve involvement. Prompt evaluation and treatment of PCNSL are essential for improving the visual outcomes of patients.
PubMed: 37131560
DOI: 10.7759/cureus.36969 -
BMJ Open Apr 2023Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central...
Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.
INTRODUCTION
Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL.
METHODS AND ANALYSIS
Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility.
ETHICS AND DISSEMINATION
This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.
TRIAL REGISTRATION
jRCTs061180093.
Topics: Aged; Humans; Antineoplastic Combined Chemotherapy Protocols; Brain; Central Nervous System; Central Nervous System Neoplasms; Clinical Trials, Phase II as Topic; Cytarabine; Lymphoma; Methotrexate; Multicenter Studies as Topic; Prospective Studies; Rituximab; Treatment Outcome; Vincristine
PubMed: 37094899
DOI: 10.1136/bmjopen-2022-071350 -
Acta Medica Indonesiana Jan 2023Primary CNS Lymphoma (PCNSL) is a rare form aggressive extra nodal non-Hodgkin Lymphoma (NHL) that comprising 1-2% of the primary brain tumors that develops in...
Primary CNS Lymphoma (PCNSL) is a rare form aggressive extra nodal non-Hodgkin Lymphoma (NHL) that comprising 1-2% of the primary brain tumors that develops in the brain, spinal cord, eye or leptomeningeal area without evidence of systemic involvement. The overall incidence of PCNSL with immunocompetent patients is only 0,47/100.000 year in PCNSL. Approximately 10-20% of patients have ocular involvement and around one third have multifocal neurological disease. Overall long-term survival rate only 20-40%, this is because the management of PCNSL is limited to ability of the drug due to cross the blood brain barrier (BBB). We present a B-cell central nervous system lymphoma in an immunocompetent patient who treat responses with chemotherapy. A 35-year-old man presented to our hospital with suddenly unconscious 4 hours before admission. He was experiencing headache and blurred of vision withing 3 months and have episode seizure. On Examination, GCS E2 M3 Aphasia, Hemiparesis dextra, papil edema, VOD/VOS: NLP. The other physical exam was normal. Laboratory tests Hb 10,7 g/dl, LDH 446 U/L, and D-dimer 3,21ug/ml. Rubella IgG 76,9, CMV Ig G 245,6 and, HSV IgG and IgM negative, HIV test non-reactive, Toxoplasma IgG and Toxoplasma IgM negative, HbsAg and HCV test negative. Brain MRI and MRI Spectroscopy: Lobulated mass size 7,08 cm x 4,75 cm at caudates nucleus sinistra-periventricular lateralis sinistra, Cholin/NAA ratio: 5-9, Cholin/Creatin ration 6-11 suspect malignancy dd/Lymphoma. MRI whole spine: Bulging discus intervertebral C4-C5. Chest and Abdomen CT-Scan are normal. Bone Survey normal, EEG: Epileproform left temporal. Cerebrospinal Fluid: Gliosis reaction sup malignancy.The patient underwent craniotomy and biopsy Pathology Anatomy and IHC Basal Ganglia revealed a Diffuse Large B Cell Lymphoma (NHL) Non-Germinal Center, CD 20 +, Ki 67 95% (High Grade), CD 45 +, CD 3 -, BCL6 +, Mum 1+. The patient we give induction therapy with RMP Regimens (Rituximab 375 mg/m2, day 1, 15 and 29, High Dose Methotrexate (HDMTX) 3000mg/m2 day 2, 16 and 30, and Procarbazine 60mg/m2 day 3-12) because Procarbazine in not available in Palembang we change to Dacarbazine 375mg/m2 days 3,17 and 31), Dexamethasone 5mg/6 hours, and has finished Low Dose Whole Brain Radiotherapy for consolation therapy. PCNSL is rare form aggressive extra nodal NHL, especially in Immunocompetent patient. In this particular case of patients High Dose Methotrexate Chemotherapy has achieved high respond especially for this patient that showed GCS E4M5V6 and recovery neurological deficit after 2 cycle chemotherapy.
Topics: Male; Humans; Young Adult; Adult; Methotrexate; Central Nervous System Neoplasms; Procarbazine; Antineoplastic Combined Chemotherapy Protocols; Lymphoma, Non-Hodgkin; Lymphoma; Brain; Immunoglobulin G; Immunoglobulin M
PubMed: 36999259
DOI: No ID Found -
American Journal of Hematology Jun 2023There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We...
There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.
Topics: Humans; Aged; Middle Aged; Aged, 80 and over; Rituximab; Methotrexate; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Activities of Daily Living; Retrospective Studies; Temozolomide; Lymphoma; Central Nervous System; Central Nervous System Neoplasms
PubMed: 36965007
DOI: 10.1002/ajh.26919 -
Cancer Discovery Apr 2023We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors of pediatric cancer with a median follow-up time of 23.5...
UNLABELLED
We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors of pediatric cancer with a median follow-up time of 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations in 15% of the survivors, significantly higher than the 8.5% in 324 community controls. CH in survivors is associated with exposures to alkylating agents, radiation, and bleomycin. Therapy-related CH shows significant enrichment in STAT3, characterized as a CH gene specific to survivors of Hodgkin lymphoma, and TP53. Single-cell profiling of peripheral blood samples revealed STAT3 mutations predominantly present in T cells and contributed by SBS25, a mutational signature associated with procarbazine exposure. Serial sample tracking reveals that larger clone size is a predictor for future expansion of age-related CH clones, whereas therapy-related CH remains stable decades after treatment. These data depict the distinct dynamics of these CH subtypes and support the need for longitudinal monitoring to determine the potential contribution to late effects.
SIGNIFICANCE
This first comprehensive CH analysis in long-term survivors of pediatric cancer presents the elevated prevalence and therapy exposures/diagnostic spectrum associated with CH. Due to the contrasting dynamics of clonal expansion for age-related versus therapy-related CH, longitudinal monitoring is recommended to ascertain the long-term effects of therapy-induced CH in pediatric cancer survivors. See related commentary by Collord and Behjati, p. 811. This article is highlighted in the In This Issue feature, p. 799.
Topics: Humans; Child; Clonal Hematopoiesis; Hematopoiesis; Mutation; Hodgkin Disease; Survivors
PubMed: 36751942
DOI: 10.1158/2159-8290.CD-22-0956 -
JAMA Oncology Apr 2023Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy....
IMPORTANCE
Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear.
OBJECTIVE
To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.
DESIGN, SETTING, AND PARTICIPANTS
A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022.
EXPOSURES
Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.
MAIN OUTCOMES AND MEASURES
Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored.
RESULTS
The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose.
CONCLUSIONS AND RELEVANCE
This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.
Topics: Male; Humans; Child; Female; Hodgkin Disease; Procarbazine; Case-Control Studies; Survivors; Colorectal Neoplasms
PubMed: 36729438
DOI: 10.1001/jamaoncol.2022.7153