Radiotherapy at tumor recurrence in primary CNS lymphoma.
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Adult↗
Biomedical subjects
A Boiardi
Publications and source records attributed to A Boiardi.
Primary cerebral non-Hodgkin's lymphoma (PCNSL): a review of new trends in management.
Primary central nervous system lymphoma (PCNSL) is a rare tumor but it is rising in incidence in both AIDS and non AIDS populations. It is a non-Hodgkin's lymphoma that usually presents itself as a brain tumor, but leptomeninges, eyes and also spinal cord are frequently affected. The management of PCNSL patients has evolved in the last years. The role of surgery has been restricted for diagnosis only because the exeresis of the tumor is ineffective owing to its multifocal and infiltrative nature. Therefore, stereotactic biopsy is the way of choice for documenting the diagnosis. The standard treatment was radiotherapy started after diagnosis and followed by chemotherapy at recurrence. PCNSL is radiosensitive and chemosensitive: about 70% of patients respond to one or other of these treatment modalities but usually PCNSL recurs locally after radiotherapy. More recently the inclusion of high doses ARA-C and Methotrexate delivered prior radiotherapy have shown significant high responses and prolonged survivals.
Brain Neoplasms↗
Advantage of treating anaplastic gliomas with aggressive protocol combining chemotherapy and radiotherapy.
We devised a treatment protocol for anaplastic gliomas consisting of:(a) chemotherapy prior to radiotherapy (b) a second chemotherapy regimen at tumor recurrence (c) repeated surgery whenever possible. 41 Anaplastic Astrocytoma (AA), 16 Anaplastic oligoastrocytoma (AOA) and 14 anaplastic oligodendroglioma (AOD) patients were treated. After surgery all patients received 5-6 cycles of carmustine+Cisplatinum chemotherapy. Radiotherapy was started during the last 2-3 cycles of chemotherapy. 17 patients (30.5%) were reoperated on at recurrence. All recurring patients underwent PVC chemotherapy. At this moment disease recurred in 56 patients. Median TTP was 24.5, 38.7 and 58.2 months for AA, AOA and AOD respectively. Median ST was 38.8, 71.8 and 73 months. In conclusion our sandwich protocol of prior chemotherapy, overlapping irradiation with second chemotherapy and, in favourable cases, a second surgical intervention, is of benefit in patients with anaplastic gliomas.
Adolescent↗
Quality of life in brain tumor patients.
With the aim of evaluating the quality of life (QL) of 101 brain tumor patients, a multidimensional approach was adopted, using the Functional Living Index-Cancer (FLIC) as a global measure of well-being, the Karnofsky Performance Scale (KPS) and the Index of Independence in Activity of Daily Living (ADL) as indices of physical and functional dimensions, the State-Trait Anxiety Inventory (STAI) and the Self-Rating Depression Scale (SRDS) for psychological assessment, and neuropsychological tests for abstract reasoning, attention, memory and frontal lobe functions. The patients were grouped on the grounds of disease stage and treatment. The FLIC and KPS ratings increased from the patients who had just undergone surgery to patients who were disease-free after completing chemotherapy and radiotherapy, thus showing that the QL may improve during the disease despite aggressive treatments, providing there is no tumor recurrence. However, only the FLIC consistently discriminated the patients' stratification. The ADL revealed no between-group differences, whereas the STAI and SRDS revealed the presence of emotional troubles at the beginning and at the end of treatment. Cognitive impairment was more serious after radiotherapy and chemotherapy, as well as in patients with tumor recurrence. The FLIC significantly correlated with all of the other scales used, showing that it is useful in summarizing both the physical and psychosocial impairment of brain tumor patients. Of the pathological variables, a tumor location in the anterior right hemisphere or diencephalon was associated with high FLIC ratings, may be due to the minor cognitive impairment observed in patients with these tumor sites. Of the demographic variables, the level of education was associated with high FLIC ratings, thus highlighting the role of psychosocial environment in improving the QL. The use of a multidimensional approach or a global index of well-being that also reflects psychosocial and cognitive aspects proved to be more appropriate than traditional functional instruments (such as the KPS) in assessing the QL of brain tumor patients and in detecting the extent of the disease.
Adult↗
Interstitial chemotherapy with mitoxantrone in recurrent malignant glioma: preliminary data.
We undertook a phase I-II trail of loco-regional mitoxantrone in 12 patients affected by malignant gliomas. Mitoxantrone was delivered at tumor recurrence by Ommaya reservoir, with 2 cycles and a 1 month interval between each cycle, in conjunction with systemic chemotherapy (8 pts) or not (4 pts). Treatment tolerability was good, and 9 of the patients showed either response or stable disease at the end of the treatment schedule. Regardless of associated chemotherapy, time to further tumor progression was at 6 months. A combination of early systemic and loco-regional chemotherapy with surgery and radiotherapy seems worth while pursuing in the therapeutic approach to malignant gliomas.
Adult↗
Intrathecal immunotherapy in CNS tumors disseminating via CSF: preliminary evaluation using different treatment schedules.
Eight patients affected by central nervous system tumours disseminating via cerebrospinal fluid received rIL-2 immunotherapy according to three different protocols involving intrathecal administration followed or not by systemic infusion. Immunological monitoring included serial evaluation of CSF leukocytes, CSF and peripheral blood CD3-CD56+ cells, and NK activity. The most marked rise in CSF leukocyte levels was induced by daily intrathecal rIL2 administration, which also induced increased PB NK activity. Systemic rIL2 infusion following intrathecal treatment maintained a high percentage of CSF CD3-CD56+ cells, but not CSF leukocytes at high levels. Clinical conditions improved after treatment in two patients, worsened in one and remained substantially unchanged in the remaining five. The side effects of intrathecal rIL2 treatment included fever, confusion, and seizures, and there were marked interindividual variations in the immunological response.
Adolescent↗
M-Bacod as first treatment for primary CNS lymphoma.
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Adult↗
Characterization of an established human, malignant, glioblastoma cell line (GBM) and its response to conventional drugs.
A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to conventional drugs. The GBM cell line exhibited a 73 +/- 7 h doubling time in monolayer cultures. Expression of glial fibrillary acidic and S-100 proteins was observed. Karyotype analysis of GBM cells at early passages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements; a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic properties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retained during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comparable to that found in cells of a different tumor type. GBM cells were found positive for the epidermal growth factor receptor, HER2-neu and P-glycoprotein by flow cytometry of cells labelled with monoclonal antibodies. In spite of the expression of relatively high gamma-glutamyltransferase activity, the intracellular glutathione level was comparable to that of other chemosensitive tumor cells. This glioblastoma cell line is a suitable model for the identification and preclinical studies of new agents and provides an additional system to explore the molecular basis of the intrinsic drug resistance of glioblastoma.
Animals↗
Loco-regional immunotherapy with recombinant interleukin-2 and adherent lymphokine-activated killer cells (A-LAK) in recurrent glioblastoma patients.
Nine patients with recurrent glioblastoma were given autologous adherent lymphokine-activated killer (A-LAK) cells and interleukin-2 (IL-2) administered directly into the tumor cavity through an Ommaya tube placed during surgery/biopsy. The immunotherapy was well tolerated and the response rate was 33% (one complete response, two partial responses, four with stable disease and two with progressive disease). However, survival 18 months from initial diagnosis did not differ from that reported in the literature for patients treated conventionally. Serial determinations of IL-2 in the tumor cavity during the course of treatment revealed that IL-2 concentrations were sufficient to maintain lymphocyte activation. Since steroid medication was discontinued during treatment and A-LAK cells have greater antitumor activity than standard LAK cells, other factors are discussed that might explain the limited results.
Adult↗
Cognitive impairment and quality of life in long-term survivors of malignant brain tumors.
Thirtysix long-term survivors following the treatment of a malignant supratentorial brain tumor were examined for cognitive functions and global level of autonomy. Eighteen patients were symptom-free (SF) and 18 had clinical and neuroradiological recurrence (RE). The control group included 30 healthy subjects. All subjects underwent a neuropsychological battery for general and specific cognitive functions. The level of autonomy was assessed by means of the Karnofsky Performance Scale (KPS) for oncological patients. SF patients showed less impairment than RE patients both at the tests, as well as on the KPS. The cognitive deficits were subclinical in most SF patients, the tests for attention, memory and word fluency being the most sensitive in detecting subtle dysfunctions. The association between tumor location and specific cognitive deficits was inconstant in both patient groups. The results suggest that even subtle cognitive deficits can prevent SF long-term survivors from returning to premorbid autonomy and occupations, and that neuropsychological tests may be used as complementary routine indicators of their quality of life. Furthermore, our data show that, in selected patients, combined treatments and therapeutic insistence do not necessarily have the same deleterious effects.
Adolescent↗
Successful adoptive immunotherapy with lymphokine-activated killer cells in the treatment of medulloblastoma disseminated via cerebrospinal fluid: case report.
We report the case of a girl who developed cerebellar medulloblastoma at the age of 12 years and in whom, 4 years after surgical removal and radiotherapy, neoplastic dissemination via the cerebrospinal fluid took place. After only partially effective systemic and intrathecal chemotherapy, an intrathecal administration of lymphokine-activated killer cells and recombinant interleukin-2 allowed complete clinical recovery persisting after a follow-up of 30 months.
Adult↗
Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.
The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.
Adult↗
Chemotherapy as first treatment for primary malignant non-Hodgkin's lymphoma of the central nervous system preliminary data.
Non-Hodgkin's lymphoma of the central nervous system (NHL-CNS) is thought to account for about 1% of primary brain tumours. Radiation therapy has mainly been applied to treat cerebral lymphoma, but the low cure rate and the lack of enduring response have stimulated the search for alternatives. With the aim of postponing radiotherapy as long as possible, we tested the efficacy of a M-BACOD schedule administered immediately after histological diagnosis in 14 patients. After two M-BACOD courses 10 (71%) patients displayed an objective response (i.e. were apparently tumour-free when examined by CT). In 6 (60%) M-BACOD-responsive patients, radiotherapy was delayed for 5 months (without recurrences after a follow-up ranging from 9 to 18 months). Moreover, in 3 M-BACOD-responsive patients, no recurrence took place (even without radiotherapy) after a follow-up of 6-12 months. We conclude that radiation can be postponed after chemotherapy or delayed until tumor recurrence.
Adult↗
Factors, including transforming growth factor beta, released in the glioblastoma residual cavity, impair activity of adherent lymphokine-activated killer cells.
Adherent lymphokine-activated killer (A-LAK) cells were obtained from peripheral blood lymphocytes of patients with recurrent glioblastoma. In vitro features of A-LAK cultures were assessed in comparison to those of non-adherent lymphokine-activated killer (NA-LAK) cells of the same patients with regard to cytotoxic activity, proliferation and surface markers. Only in a minority of cases did A-LAK cells show a markedly higher cytotoxicity on K562, Daudi and allogeneic glioblastoma cells. Nevertheless, A-LAK cells proliferated significantly better than NA-LAK and contained higher percentages of CD16+, CD56+ and CD25+ cells, indicating that A-LAK cells from these patients represent a subpopulation of lymphocytes enriched for activated natural killer cells. We also investigated whether immunosuppressive factor(s) were present in the tumour bed of recurrent gliomas. To this end, samples of glioblastoma cavity fluid (GCF), which accumulates in the cavity of subtotally removed tumour, were recovered and tested for the presence of immunosuppressive activity. All GCF samples analysed were shown to inhibit in vitro proliferation and antitumour cytotoxicity of 1-week-cultured A-LAK cells in a dose-dependent manner. Such GCF activity was effectively antagonized by a transforming growth factor beta (TGF beta) neutralizing antibody, indicating the involvement of TGF beta in lymphocyte inhibition. These results show that in the tumour cavity remaining after subtotal glioblastoma resection a marked immunosuppressive activity, probably due to local release of TGF beta, is present; such activity may negatively influence the therapeutic effectiveness of local cellular immunotherapy.
Cell Adhesion↗
Efficacy of '8-drugs-in-one-day' combination in treatment of recurrent GBM patients.
Thirty-five adult recurrent GBM patients, divided randomly in two groups of 19 and 16 cases, had been treated with two regimens of chemotherapy: a) 'eight-drugs-in-one-day'; b) procarbazine + CCNU + vincristine (PCV) respectively. Chemotherapy was planned at the tumour relapse and delivered as long as tolerated without irreversible sequelae or until the CT scan showed tumor progression. Multiple agents are used simultaneously in the therapeutic approach using 'eight-in-one' to kill as many heterogeneous cells of malignant glial tumor as possible and minimize the emergence of cellular resistance to chemotherapy. Rate response to chemotherapy and the median adjunctive survival time (6.5 and 6 months, respectively) are not significantly different in the two arms of this study. Our experience with such an aggressive multi-drugs combination 'eight-in-one-day' was disappointing if compared with less toxic, better tolerated and easy delivered (PCV) regimen.
Antineoplastic Combined Chemotherapy Protocols↗
Peripheral nerve involvement in Churg-Strauss syndrome.
Peripheral neuropathy associated with bronchial asthma, multisystem organ dysfunction and idiopathic hypereosinophilia may be found in Churg-Strauss syndrome, hypereosinophilic syndrome and polyarteritis nodosa. Some authors have diagnosed their patients according to the presence in tissue biopsies of the three histological criteria of Churg and Strauss (necrotizing vasculitis, tissue eosinophilic infiltration, extravascular granulomas). We have observed three patients with a common history of a prodromal phase of allergic diseases (bronchial asthma and rhinitis) followed by a vasculitic phase with mononeuritis multiplex, purpura and arthritis, associated with hypereosinophilia of more than 1500 cells/mm3. All responded well to steroid treatment. Sural nerve biopsy revealed true vasculitis in two of these cases and a mild perivascular inflammatory infiltration in the other. On the basis of their characteristic clinical pattern, we think that our cases best fit the diagnosis of Churg-Strauss syndrome even though the typical histological features were not found in the sural nerves examined.
Adolescent↗
Cisplatin neuropathy in brain tumor chemotherapy.
38 patients with glial brain tumors received 135 mg/m2 cisplatin intravenously every month for 5 courses. Signs and symptoms of peripheral neuropathy were evaluated clinically and electrophysiologically. This approach differs from methods previously reported in that it offers two major advantages: primary brain tumors do not cause paraneoplastic neuropathy; no neurotoxic drugs other than cisplatin were employed. Our study confirmed in this highly specific clinical model the existence of cisplatin peripheral neuropathy: we observed definite clinical signs or symptoms of neuropathy in 80% of patients receiving a cumulative cisplatin dosage of 675 mg/m2; there was a progressive dose-related decrease in SAP amplitudes, expression of a sensory axonopathy or neuronopathy.
Adult↗
Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma.
The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cisplatin, carboplatin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP + VP-16; (C) CBDCA + BCNU; (D) CBDCA + BCNU + VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.
Adult↗