Marcel Odaimi

Treatment of Recurrent Glioblastoma Multiforme Using Fractionated Stereotactic Radiosurgery and Concurrent Paclitaxel

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.

Adoptive cellular immunotherapy for the treatment of malignant gliomas.

UNLABELLED The median survival for adults with recurrent primary malignant gliomas is 56 weeks following surgery, radiation, and chemotherapy. Generally, reoperation can extend the median survival an additional 26-32 weeks. We have developed an aggressive treatment program that utilizes low doses of interleukin-2 (IL-2) combined with ex vivo activated killer cells (LAK) infused via an indwelling catheter placed into the surgical resection cavity. Autologous leukocytes were collected during a standard 3-4 h, outpatient leukapheresis procedure, then activated ex vivo for 4-5 days with high doses of IL-2. The treatment protocol consisted of two 2-week cycles of therapy over a 6-week period. Patients with stable disease or objective response on follow-up MRI scans were retreated at 3-month intervals. Acute and cumulative IL-2-related toxicities were observed, but limited, and included fever, headache and transient neurologic irritation. Corticosteroid levels and usage were strictly controlled during immunotherapy, although higher doses were used intermittently to mitigate toxicity. Biologic changes included lymphocytic infiltration, regional eosinophilia, tumor necrosis, and the localized production of IL-2, IFN-gamma and IL-12, demonstrated by in situ hybridization and immunohistochemistry. SUMMARY IL-2 plus autogeneic LAK cells can be safely administered intracavitary to treat high grade primary brain tumors with limited toxicity within the central nervous system. Six out of 28 patients had long-term survival of greater than 2 years post-reoperation plus immunotherapy with 2 patients alive over 8 years. The presence of a marked regional eosinophilia appeared to correlate with increased survival and may be predictive of a biologic and therapeutic response. Regional adoptive immune therapy was well tolerated and should be considered an option for patients with high-grade tumors refractive to standard therapeutic approaches.

Fractionated stereotactic radiosurgery and concurrent taxol in recurrent glioblastoma multiforme: a preliminary report.

PURPOSE Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.

Recurrent Glioblastoma multiforme: Potential Benefits Using Fractionated Stereotactic Radiotherapy and Concurrent Taxol

UNLABELLED A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous Taxol as a radiation sensitizer. METHODS The treatment outcome was analyzed in two groups of patients with recurrent glioblastoma. Group 1 was analyzed retrospectively, and consisted of 9 patients with a median tumor volume of 9.2 cm3 treated with single-fraction stereotactic radiosurgery alone (mean radiation dose of 19.2 Gy). In group 2, prospectively analyzed, were 14 patients treated with fractionated stereotactic radiotherapy and concurrent Taxol. RESULTS The median survival in group 2 was 14.2 months versus 6.3 months in group 1 (p < 0.04). One-year survival for patients who received fractionated radiotherapy with Taxol was 50% compared to 11% for those treated with single-fraction radiotherapy only (p = 0.05). CONCLUSIONS Survival for group 2 patients was significantly better compared to those treated with single-fraction radiotherapy alone. These data should stimulate the investigation of both fractionated stereotactic radiotherapy and the development of radiation sensitizers to further enhance treatment.

A Unique Case of Malignant Pleuropericardial Effusion: HHV-8-Unrelated PEL-Like Lymphoma-A Case Report and Review of the Literature.

Primary effusion lymphoma (PEL) or body cavity lymphoma is a rare type of extra nodal lymphoma of B-cell origin that presents as lymphomatous effusion(s) without any nodal enlargement or tumor masses. It belongs to the group of AIDS related non-Hodgkins lymphomas. First described in 1996 in HIV infected individuals who were coinfected with Kaposis sarcoma-associated herpesvirus (KSHV) or HHV-8 virus, it was included as a separate entity in WHO classification of tumors of hematopoietic and lymphoid tissue in the year 2001. The definition included association with HHV-8 virus as a mandatory diagnostic criterion. However, cases were later reported where PEL-like disease process was diagnosed in HHV-8 negative patients. This was eventually recognized as a rare but distinct entity termed as “HHV-8-unrelated PEL-like lymphoma”. Herein, we are reporting a case of an elderly patient who presented with a large pleuropericardial effusion and was eventually diagnosed with this entity. Till date, only around 50 cases of HHV-8-unrelated PEL-like lymphoma have been reported and our case being EBV, HIV, and Hepatitis C negative makes it very unique and rare occurrence. We are also presenting a review of relevant literature focused mainly on comparing outcomes in patients treated with and without chemotherapy.

A 61-year-old man presented with myopathy, neuropathy, and inflammatory dermatitis responsive to chronic lymphocytic leukemia treatment

The prevalence of paraneoplastic neurologic syndrome in cancer is 0.01%. Neurological syndromes can be seen in chronic lymphocytic leukemia (CLL) and mostly present as either leukemic infiltration of the central nervous system (CNS) or progressive multifocal leukoencephalopathy. To our knowledge, this is the first reported case of combined sensory-motor neuropathy, myopathy, and dermatitis in a patient with CLL. Case presentation A 61-year-old African American man presented with acute dysphagia, rapidly progressive proximal limb-girdle weakness, and dermatitis. He had a white blood cell (WBC) count of 14,600/mm3, hemoglobin of 11.4 mg/dL, and a platelet count of 165,000/mm3. Lymphocytes comprised 15% of the total WBC with an absolute lymphocyte count of 2100/mm3. Metabolic profile was unremarkable except for a serum creatine phosphokinase (CPK) level of 1056 mg/dL. Serum protein electrophoresis, serologic studies for autoimmune, genetic diseases, and paraneoplastic syndromes were all negative. Electrodiagnostic studies revealed sensorimotor neuropathy with mixed axonal and demyelinating features. Muscle biopsy revealed discrete areas of interstitial fibrosis juxtaposed to areas of intact muscle without any inflammation. At that point, a bone marrow biopsy was done because of anemia and slightly elevated mean corpuscular volume of 103. Bone marrow biopsy revealed minimal involvement with CD5/CD19-positive CLL. Flow cytometry demonstrated monoclonal CD5/CD19/CD20/CD23-positive cells, with dim kappa expression, and negative FMC-7 and CD3. This case doesn’t meet the criteria for CLL/small lymphocytic lymphoma. However, considering the possibility of paraneoplastic phenomenon for his symptoms, it was decided to start the patient on CLL-directed therapy with Rituximab and Cyclophosphamide. After only two cycles, the patient experienced a dramatic improvement in his muscle strength with disappearance of the rash. Conclusion This case highlights a unique clinical picture of inflammatory dermatitis with electromyography and biopsy findings suggestive of myopathy and combined sensorimotor neuropathy with response to CLL-directed therapy. Also the symptoms started before peripheral lymphocytosis which masked the diagnosis for over a year.

Bleomycin-induced flagellate erythema in a patient with Hodgkin’s lymphoma – A case report and review of literature

Bleomycin is a glycopeptide used as a chemotherapeutic agent for lymphomas, germ cell tumors, and pleurodesis of malignant pleural effusions. The pulmonary toxicity of bleomycin is well known while the cutaneous side effects are uncommon and varies from generalized hyperpigmentation, sclerodermoid changes, erythema multiformae, and gangrene to flagellate dermatosis. Here we report a characteristic but rare side effect of flagellate erythema, which developed secondary to bleomycin in a 27-year old woman with Hodgkin’s lymphoma after two cycles of treatment with adriamycin, bleomycin, vinblastine, dacarbazine regimen. The rash subsided after discontinuation of bleomycin and treatment with steroids.

Achievement of Three Year Remission with Bevacizumab and Irinotecan in Recurrent Glioblastoma Multiforme: A Case Report

A 34-year-old man presented to the hospital with right-sided headache. He was diagnosed with GBM. He underwent resection of the tumor with placement of carmustine impregnated wafers. Then he underwent adjuvant chemotherapy with temozolamide. Before the completion of chemotherapy he had a recurrence. He underwent re-resection with placement of carmustine impregnated wafers. Subsequently he had eighteen cycles of salvage biochemotherapy with bevacizumab and irinotecan. To date, routine MRI scans of the brain have not shown evidence of recurrence. He continues to be in remission three years after treatment with bevacizumab and irinotecan.

A patient with multiple synchronous gliomas of distinctly different grades and correlative radiographic findings.

Background: Multiple gliomas represent approximately 2 to 5% of all high-grade gliomas which are categorized as multifocal or multicentric depending on the timing, location and pattern of spread. We present a patient with bi-hemispheric, noncontiguous, low- and high-grade gliomas proven by biopsy. She underwent surgical excision and radiotherapy, but unfortunately succumbed to her disease shortly thereafter. Case Description: A 64-year-old female presented to the hospital with confusion, disorientation and retrograde amnesia after an unwitnessed fall. There were no symptoms of headaches or visual disturbances before presentation. Magnetic resonance imaging (MRI) with and without gadolinium revealed a nonenhancing left temporal lobe mass without surrounding edema, an enhancing left frontal lobe mass with surrounding edema, and an enhancing right parietal lobe mass with surrounding edema. The patient underwent a left frontal craniotomy with gross total resection of the left frontal mass and a left temporal craniotomy, anterior temporal lobectomy and sub-total resection of the temporal lobe mass. Intraoperative Brainlab® image-guided navigation was used. Postoperative treatment consisted of radiotherapy. Conclusion: This is the first reported case of multiple separate glial tumors, each with differing grades in which an MRI can be correlated with the tissue diagnoses. This case also highlights the possible mechanisms of transformation of glial tumors in the continuum from benign to malignant forms, lending insight to the possibility of using advanced genetic analysis in the treatment and diagnosis of these entities.

Rasburicase-induced methemoglobinemia: The eyes do not see what the mind does not know:

Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.