Radioimmunotherapy (RIT) in non-Hodgkin lymphoma

Radio-labeled anti-CD20 antibodies are a relatively novel technique that uses monoclonal antibodies to target CD20-positive cells and administer complex antibody-mediated and/or complement-dependant cytotoxicity in combination with systemic radiotherapy to targeted cells and adjacent cells via the “crossfire” effect. There are currently two main agents in clinical practice—yttrium-90 (⁹⁰Y) ibritumomab tiuxetan (Zevalin) and iodine-131 (¹³¹I) tositumomab (Bexxar)—with other agents in clinical development. Studies have been performed looking into the use of radioimmunotherapy (RIT) in indolent non-Hodgkin lymphoma (NHL), initially in patients with relapsed, treatment-refractory and transformed disease (overall response rates [ORR] 74–92% with complete response [CR] 15–51%), and also in patients not suitable for transplant (i.e., the elderly population [CR 23%]) and in isolation in the first-line setting (comparable response rates to RCHOP) and combination with chemotherapy in the first-line setting (ORR 90–100%). The use of RIT in diffuse large B cell aggressive (DLBC) NHL has been assessed initially in patients with relapsed disease, both rituximab naïve (ORR 44%) and refractory (ORR 19%), and more recently as consolidative treatment following primary chemotherapy (early results 5-year overall survival 60% vs 37%), or in combination with primary chemotherapy. The main side effects are infusion related and hematological with a delayed nadir (4–6 weeks in DLBC NHL, 6–8 weeks in indolent disease) and correlate with bone marrow reserve.     

Ibritumomab tiuxetan for non-Hodgkin’s lymphoma

Targeted radiation therapy, or radioimmunotherapy, has been an important recent advancement in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL). ⁹⁰Y ibritumomab tiuxetan comprises the murine monoclonal antibody ibritumomab, the linker chelator tiuxetan and the radiolabeled isotope ⁹⁰yttrium. ⁹⁰Y ibritumomab tiuxetan has been demonstrated to be efficacious in the treatment of B-cell NHL. Initial Phase I/II trials established the therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or 0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many ongoing trials of ibritumomab tiuxetan with different dose schedules and intensities, in combination with chemotherapy and with stem cell transplantation, in an attempt to improve response rate and duration and to study its effectiveness in other B-cell lymphomas, including diffuse large B-cell lymphoma and mantle cell lymphoma. Radioimmunotherapy has great promise and the safe incorporation of ⁹⁰Y ibritumomab tiuxetan into treatment will hopefully result in improved survival for patients with NHL.     

Comparative analysis of [3H]-thymidine labelling index and monoclonal antibody Ki-67 in non-Hodgkin's lymphomas

The relation between the [³H]-thymidine labelling index (3H-Thy LI), which evaluates the S-phase cells, and the monoclonal antibody Ki-67 (MoAb Ki-67), which recognizes a nuclear antigen expressed during the cell cycle, was defined in 35 non-Hodgkin's lymphomas (NHL). Significantly higher median values of [³H]-Thy LI and Ki-67-positive cells were observed for high-grade than for low-grade malignancy tumours according to the Kiel classification, but with wide and overlapping values for the two morphologic subgroups. A significant correlation was observed between [³H]-Thy LI and Ki-67-positive cells (P < 0.0001; r = 0.62). However, the ratio between the two cell kinetic variables on individual tumours was not constant. It sharply increased with decreasing [³H]-Thy LI values and was much higher in low-grade NHL than in high-grade NHL. Follow-up studies are needed to establish the role of the tumour growth fraction as evaluated by MoAb Ki-67 as a prognostic indicator in NHL.     

MACOP-B and involved field radiation therapy is an effective therapy for primary mediastinal large B-cell lymphoma with sclerosis

Purpose: To evaluate the clinical features of presentation and the response to two different third-generation regimens (F-MACHOP and MACOP-B) of primary mediastinal large B-cell lymphoma (MLBCL), a recently defined distinct clinicopathological entity of non-Hodgkin's lymphoma (NHL).Patients and methods: Thirty-seven consecutive patients with MLBCL, eight male and 29 female (F/M ratio 1 : 3.5) with a median age of 35 years, were enrolled in the present study.Thirty-five (94.5%) patients presented disease confined to thorax,with chest symptoms of a rapidly enlarging mass in the mediastinum in 70% and superior vena cava syndrome (SCVS) in 43% of these patients. The first 10 patients received F-MACHOP and the succeeding 27 patients MACOP-B chemotherapy, associated in 24 (88.8%) with involved field radiation therapy (IFRT). ⁶⁷Gallium scan was routinely performed pre- and post-IFRT in 18 patients.Results: All 37 patients were assessable for response: 10 of 10 (100%) in the F-MACHOP and 26 of 27 (96.3%) in the MACOP-B group achieved overall responses (CR+PR). Three of 24 (12.5%) patients in PR after chemotherapy obtained CR after IFRT. Persistent Gallium avidity was observed in 16 patients after chemotherapy and in only four patients after IFRT. Thus far, four of the 10 F-MACHOP and two of the 26 MACOP-B responders have presented disease progression. The probability of progression-free survival (PFS) was 91% and 60% (P < 0.02) while overall survival (OS) was 93% and 70% (P = n.s.) at a mean follow-up of 27 and 52 months in the MACOP-B+IFRT and F-MACHOP groups, respectively.Conclusion: MACOP-B+IFRT has proved to be a highly effective and less toxic therapeutic approach for primary MLBCL and appears to be superior to other third-generation chemotherapy regimens.     

Hypophyseal Non-Hodgkin's Lymphoma Presenting with Diabetes Insipidus: A Case Report

We report the case of a 64 year old male patient with a history of ischemic heart disease who underwent surgery for an abdominal mass. The histological diagnosis was highly malignant non-Hodgkin's lymphoma. After surgery the patient was admitted to our Department and received 6 courses of chemotherapy according to the COP schedule, followed by radiotherapy to the left upper abdominal region and ipsilateral lung base. The patient achieved partial remission. One month later he began to complain of left axillary lymphadenomegaly, polydipsia and polyuria. A NMR brain scan showed a hypophyseal mass. The patient was treated with DDAVP and chemotherapy with the PRO-MACE protocol; the polyuria and lymphadenomegaly disappeared and the size of the hypophyseal mass reduced markedly. The clinical picture was, therefore, attributed to a hypophyseal localization of the non-Hodgkin's lymphoma, which is a very rare manifestation of lymphomatous spread to the central nervous system. Our case is also interesting because it shows that a favorable outcome can be obtained with chemotherapy, provided that the latter is sufficiently aggressive. This is not necessarily the case with radiotherapy which may also be followed by late and severe neurologic sequelae.     

Use of 201Tl SPECT Imaging to Assess the Response to Therapy in Patients with High Grade Gliomas

Purpose. To assess the potential role of ²⁰¹Tl single photon emission tomography (201-Thallium SPECT) when compared to other imaging modalities in the evaluation of the response to therapy in high grade gliomas. Materials and methods. Twenty patients with histologically proved high grade glioma have been included: 15 with glioblastoma (GBM), 3 with anaplastic astrocytoma (AA) and 2 with anaplastic oligoastrocytoma (AOA). Patients were assessed by ²⁰¹Tl SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) at (a) either at the moment of maximum response to first line chemotherapy, or after the completion of radiotherapy and chemotherapy if post-surgical residual disease was present, and (b) after the completion of second line chemotherapy if disease persisted, or either a relapse or disease progression was confirmed. Final response was evaluated according to the McDonald criteria, and by comparing SPECT, CT and MRI results. Results. According to the McDonald criteria, clinical response after first line chemotherapy was 5 partial response, 7 stable disease and 8 progressive disease. Evaluation by ²⁰¹Tl SPECT was in agreement with such criteria in nearly all patients (90%). MRI findings closely agreed with the clinical follow-up. CT findings clearly differed from those observed by SPECT and MRI. After second line therapy, 10 patients progressed, 3 had stable disease and 7 had partial response. ²⁰¹Tl SPECT agreed with the clinical status in 89% cases, whereas MRI and, specially CT, fared significantly lower. Conclusion. Compared to conventional neuroimaging, ²⁰¹Tl SPECT added valuable information in the assessment of the response to therapy in our patient population; whenever findings were not conclusive and in the case of disagreement between CT and MRI findings.     

Progressive Intermediate-Grade Non-Hodgkin's Lymphoma After High-Dose Therapy and Autologous Peripheral Stem-Cell Transplantation: Changing the Natural History with Monoclonal Antibody Therapy

The prognosis of patients with progressive intermediate-grade non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous peripheral stem-cell transplantation (PSCT) is poor, with survival measured in months. The advent of monoclonal antibody therapy for NHL has created new options for effective therapy with relatively mild side effects. We report on two patients with progressive intermediate-grade NHL after PSCT who were treated with monoclonal antibody therapy. Both patients initially received rituximab (unlabeled anti-CD20 monoclonal antibody) and were subsequently treated with ⁹⁰Y-epratuzumab (yttrium-90—labeled humanized anti- CD22 monoclonal antibody) at relapse. One patient received ⁹⁰Y-epratuzumab alone while the other was treated with higher doses in combination with autologous peripheral stem-cell infusion. Both patients achieved a rapid response to the radiolabeled antibody with minimal toxicity. Monoclonal antibody therapy may be an effective and tolerable treatment for progressive NHL after PSCT.     

201Thallium SPECT and 1H-MRS Compared with MRI in Chemotherapy Monitoring of High-grade Malignant Astrocytomas

Purpose To compare chemotherapy treatment monitoring in astrocytoma by ²⁰¹thallium single photon emission computed tomography (SPECT) and photon magnetic resonance spectroscopy (¹H-MRS) with magnetic resonance imaging (MRI), and to evaluate the influence of morphological tumor changes on cerebral ²⁰¹thallium uptake and metabolic changes in ¹H-MRS. Materials and methods Six patients with highly malignant astrocytomas were followed with quantitative ²⁰¹thallium SPECT, MRI, and ¹H-MRS during chemotherapy. Maximum follow-up included six examinations per patient by either method during 18 months. Criteria were set for: (1) regression ( 25% tumor reduction), (2) status quo (< 25% reduction and < 25% increase), and (3) progression of disease ( 25% tumor increase). Results were compared with the clinical state of disease. Changes of tumor volume, contrast enhancement, necrosis, hemorrhage and edema on MRI were compared to changes in ²⁰¹thallium uptake volumes and ¹H-MRS metabolite ratios. Results Six patients were followed with a total of twenty-four examinations with ²⁰¹thallium SPECT, MRI and ¹H-MRS, respectively, between February 1997 and October 1998. Five patients developed clinical progression of disease, 4 out of 5 cases showed SPECT progression, 4 out of 5 cases MRI progression, and 1 out of 2 interpretable cases ¹H-MRS progression at final assessment before clinical deterioration. During the phase of clinically stable disease; (A) the criterion for regression or status quo was met in 10 out of 13 assessments with SPECT, 11 out of 13 with MRI, and 8 out of 9 interpretable ¹H-MRS; (B) the criterion for progression was met in 3 out of 13 with SPECT, 2 out of 13 with MRI, and 1 out of 9 interpretable ¹H-MRS. The accuracy of SPECT, MRI, and ¹H-MRS in identifying changes of tumor burden concordant with patients' clinical course was 78%, 83%, and 82%, respectively. SPECT regression was associated with MRI decrease of tumor size, contrast enhancement, edema and hemorrhage. SPECT progression was associated with MRI increase of the same parameters and the increase of necrosis. ¹H-MRS regression was associated with decrease of edema. ¹H-MRS progression was associated with increase of tumor size, hemorrhage, and increase or decrease of contrast enhancement. Conclusions Both ²⁰¹thallium SPECT and ¹H-MRS evaluation showed sensitivity for detection of astrocytoma progression. We did not find a higher accuracy of SPECT or MRS than of MRI in astrocytoma chemotherapy monitoring. Treatment induced MRI changes were associated with ²⁰¹thallium uptake variations. ¹H-MRS was difficult to apply for astrocytoma treatment monitoring. Improvements regarding size of measurement area such as multivoxel MRS and fat suppression pulses appeared desirable, and also the use of functional techniques with superior resolution such as dual isotope SPECT. However, our results suggest that ²⁰¹thallium SPECT and ¹H-MRS can provide additional information to MRI for chemotherapy efficacy evaluation in selected cases.     

Phase II study of neoadjuvant weekly nab-paclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced HER2+ breast cancer

Purpose

Neoadjuvant treatment with chemotherapy plus trastuzumab is standard care for women with locally advanced, HER2-positive (HER2⁺) breast cancer. HER2 has been shown to stimulate angiogenesis through vascular endothelial growth factor upregulation. We investigated the feasibility and efficacy of bevacizumab in combination with trastuzumab, nab-paclitaxel, and carboplatin as neoadjuvant therapy for women with locally advanced HER2⁺ breast cancer.

Patients and Methods

Twenty-eight women with locally advanced HER2⁺ breast cancer received nab-paclitaxel (100 mg/m² intravenously [I.V.] days 1,8, and 15) and carboplatin (AUC = 6 I.V. day 1) every 28 days × 6 cycles. Concurrent with chemotherapy, trastuzumab (4 mg/kg loading dose, then 2 mg/kg) and bevacizumab (5 mg/kg I.V.) were administered weekly × 23 weeks. Patients then underwent mastectomy or breast-conserving surgery; pathologic responses were assessed. After surgery, trastuzumab 6 mg/kg and bevacizumab 15 mg/kg were administered every 3 weeks (54 weeks total); locoregional radiotherapy and/or antiestrogen therapy was administered per standard guidelines.

Results

Twenty-six patients (90%) completed neoadjuvant therapy, with objective responses in 86%. Pathologic complete response (pCR) was confirmed in 14 of the 26 patients (54%) who had surgery. However, bevacizumab-related complications were common postoperatively and during adjuvant trastuzumab/bevacizumab therapy. Ten patients had wound-healing delays or infections (6 patients discontinued therapy); 4 patients had left ventricular ejection fraction (LVEF) decreases (1 patient discontinued therapy). Other severe treatment-related toxicity was uncommon. Only 9 patients (31%) completed all protocol therapy.

Conclusions

Neoadjuvant therapy with nab-paclitaxel, carboplatin, trastuzumab, and bevacizumab was feasible in most patients, producing a pCR rate comparable to that in chemotherapy/trastuzumab combinations. In contrast, prolonged bevacizumab/trastuzumab therapy after surgical treatment was not well tolerated, primarily due to bevacizumab-related toxicity. The role of bevacizumab in neoadjuvant therapy remains undefined.     

The Prediction of HER2-Targeted Treatment Response Using 64Cu-Tetra-Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent ⁶⁴Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status. ⁶⁴Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with ⁶⁴Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate ⁶⁴Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that ⁶⁴Cu-DOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.     

Interferon-induced protein 16 expression in colorectal cancer and its correlation with proliferation and immune signature markers

Interferon-induced protein 16 (IFI16) is important for innate immune recognition of foreign/damaged DNA. Abnormal IFI16 expression is closely related to the occurrence of multiple malignant tumours, but its expression pattern in colorectal cancer (CRC) remains unclear. The present study aimed to investigated IFI16 expression and association with cell proliferation in CRC tissues and adjacent normal tissues. A multiplex immunofluorescence panel of antibodies against IFI16, Ki-67 and phosphorylated (p)-ERK1/2 was applied to assess a tissue microarray (TMA). The TMA included 77 CRC samples and 74 normal adjacent tissue samples which were collected from The First People''s Hospital of Yunnan Province (Kunming, China) (3 paracancerous tissues were lost because of repeated cutting). Immunohistochemistry was used to detect CD8⁺ tumour-infiltrating lymphocyte (TIL) abundance and programmed death-ligand 1 (PD-L1) expression in cancer tissues. The present study demonstrated that IFI16 localized to the nucleus of CRC cells. Although IFI16 was weakly expressed in normal mucosal epithelial cells, absent to strong expression was detectable in different patients with CRC. Typically, IFI16 was not co-localized with Ki-67 within CRC cells. The multiplex immunofluorescence data demonstrated that the proportion of IFI16⁻/Ki-67⁺ cells from CRC tissues was 57.13%; however, that of IFI16⁺/Ki-67⁺ cells was 1.50%. The IFI16⁻/Ki-67⁺ phenotype was significantly positively associated with the tumor-node-metastasis stage and was marginally significantly correlated with lymph node metastasis. p-ERK1/2 protein was primarily localized to the cytoplasm and cell membrane of CRC cells and sometimes to the nucleus. Although, IFI16 demonstrated a strong correlation with p-ERK1/2, IFI16 did not co-localize with p-ERK1/2 and the proportion of IFI16 and p-ERK1/2 double-negative CRC cells was 84.95%. IFI16 expression displayed no significant association with CD8⁺ TILs or PD-L1. However, a strong positive correlation between CD8⁺ TILs and PD-L1 was observed. High CD8⁺ TIL infiltration in CRC tissue was associated with lower lymph node metastasis and tumor-node-metastasis stage. In summary, the results of the present study provided a novel insight for the role of IFI16 in CRC occurrence via the regulation of cancer cell proliferation.     

Phase II study of docetaxel and topotecan combination chemotherapy in patients with advanced head and neck cancer

Purpose To evaluate the activity of combination chemotherapy with docetaxel and topotecan in patients with advanced head and neck cancer.Methods Docetaxel was given at 60 mg/m² as a 60-min intravenous infusion on day 1. Topotecan at 0.75 mg/m² per day was infused over 30 min on days 1, 2 and 3. Cycles were repeated every 21 days.Results There were no responses (CR+PR) seen in the ten patients. Only one patient had stable disease and was able to receive six cycles of chemotherapy. Median survival was 81 days (range 67–161 days).Conclusions The combination of docetaxel and topotecan at these doses and in this schedule is not recommended for patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Other investigational approaches are needed.     

卵巢癌P-糖蛋白、GST-π、P53、P185表达对近期化疗效果的影响

 目的:评价卵巢癌P-糖蛋白、P53、P185表达对近期化疗效果的影响及相互关系。方法:免疫组织化学ABC法检测49例卵巢癌P-糖蛋白、GST－π、P53、P185表达。结果:1.卵巢癌P-糖蛋白、GST－π、P53、P185表达阳性者的近期化疗有效率分别为14.3％。27.3％、41、67％、24、63％,而表达阴性者的近期化疗有效率分别为53.6％(P0.05)、75.0％(P<0.005)。2.P-糖蛋白、P185的表达存在相关性(P＜0.05)。结论:卵巢癌P-糖蛋白、GST－π、P185的表达明显影响其近期化疗效果。P-糖蛋白、P185表达的相关性值得进一步研究。     

Outcome of treating advanced neuroendocrine tumours with radiolabelled somatostatin analogues

Objectives  To evaluate the initial response and outcomes (quality of life and presence of side effects) in patients with advanced neuroendocrine tumours (NET) after treatment with radiolabelled somatostatin analogues: ⁹⁰Y-DOTAT-yr3-octreotide (⁹⁰Y-DOTATOC) and ¹⁷⁷Lu-DOTA-Tyr3- octreotate (¹⁷⁷Lu-DOTATATE). Material and methods  The study included 5 patients with advanced NET referred to European centres for treatment with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE after lack of response to conventional treatment. The mean age was 45.6 years (29-68 years). Response to therapy was assessed according to: (1) RECIST criteria, as complete response, partial response, stable disease or disease progression, (2) post-treatment survival time and (3) quality of life, using the Karnofsky performance index. Results  All patients survived for >20 months after treatment; mean survival time was 28 months. At the time of writing, three of the patients are alive after 20, 26 and 37 months. Partial response was observed in one patient, stable disease in three and disease progression in the fifth patient. A good-to-excellent post-treatment quality of life was observed in all patients. Conclusion  Therapy with radiolabelled somatostatin analogues showed promising results in patients with advanced NET, with a partial response or disease stabilisation in four of the five patients, who have enjoyed an extended survival period and an improved quality of life.     

Hepatitis B virus reactivation in adjuvant chemotherapy for breast cancer

Immunosuppressive therapy, such as chemotherapy or the use of corticosteroids, may stimulate reactivation of hepatitis B virus (HBV). Most of these episodes occur in patients whose hepatitis B surface antigens are positive (HBsAg+). We report a case of HBV reactivation in a patient with negative HBsAg during chemotherapy for breast cancer, in spite of avoiding corticosteroids. A 68-year-old woman received adjuvant chemotherapy for breast cancer. Her serological examinations showed that HBsAg, HBeAg, and HBV-DNA were all negative. Her chemotherapy consisted of CAF (cyclophosphamide 500 mg/m², doxorubicin 50 mg/m², fluorouracil 500 mg/m²) without administration of corticosteroids. She received six cycles of CAF. At day 27 after her sixth CAF, she was admitted to the hospital with acute hepatitis B virus (HBV) reactivation. She received glycyrrhizinic acid by intravenous injection (80 mg/day), ursodeoxycholic acid (300 mg/day), and entecavir (0.5 mg/day). Then she received interferon by intravenous injection (3 million units/day), prednisolon by intravenous injection (45 mg/day), and plasma exchange therapy. However, she died of liver failure. This is a rare case in which HBV reactivation occurred in an HBsAg negative patient during chemotherapy without using corticosteroids. This episode suggests that HBV reactivation may occur during chemotherapy in any patient with a history of HBV infection. Therefore, we recommend checking HBsAg, HBsAb, and HBcAb before starting chemotherapy. Moreover, with positive HBsAb or/and HBcAb patients, HBV-DNA should be checked before starting chemotherapy and monitored during chemotherapy by a sensitive PCR method.     

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone,etoposide, ifosfamide,and cisplatin

Summary A total of 30 consecutive patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) were treated with a combination of dexamethasone, etoposide (VP-16), ifosfamide, and cisplatin (DVIP). In all, 9 subjects (30%) showed a partial response and 10 (33%) achieved a complete response (CR) lasting from 2.5 to 24+ months. Aggressive histology, no prior therapy with VP-16, a CR to previous chemotherapy, and a treatment-free interval of >6 months prior to the present study were associated with the high CR rate. DVIP caused pronounced myelosuppression (median granulocyte nadir and median platelet nadir, 380/mm³ and 73.000/mm³, respectively), but no drug-related death occurred. We conclude that DVIP is an effective salvage combination, especially in aggressive NHL, that produces acceptable toxicity.Presented in part during the 15th Congress of the European Society for Medical Oncology, Copenhagen, Denmark, November 1990     

Pentavalent technetium-99m dimercaptosuccinic acid [<Superscript>99m</Superscript>Tc-(V)DMSA] brain scintitomography—a plausible non-invasive depicter of glioblastoma proliferation and therapy response

The biological behavior and prognosis of gliomas depend largely on cellular proliferation, resistance to chemotherapy, and metastatic potential. Proliferative propensity has significant implications on patient management but its assessment requires tissue sampling; the non-invasive estimation of brain tumor proliferation represents therefore a major goal. Pentavalent technetium-99 m dimercapto-succinic acid [^99mTc-(V)DMSA] is a tumor-seeking radiotracer displaying affinity for gliomas; its intracellular accumulation is directly linked to cell proliferation. We performed a tomographic ^99mTc-(V)DMSA brain scan in a 35-year-old male baring a recurrent glioblastoma multiforme, to depict its proliferative disposition. The patient had been diagnosed 14 months earlier and had been submitted to surgery, followed by adjuvant radiotherapy and temozolomide-based chemotherapy. On clinical suspicion of recurrence 5 months later, magnetic resonance imaging (MRI) revealed a lesion at the site of preceded surgery, which was treated by imatinib mesylate. No improvement was ascertained the following months and radiographic assessment verified tumor progression. Scintitomography revealed avid radiotracer uptake in the entirety of the lesion (the distribution of radioactivity closely conforming to the morphological tumor boundaries), an indication that the neoplasm demonstrated no substantial proliferation decline in response to imatinib. The patient deceased a few weeks later. Mounting in vivo and in vitro evidence indicates that ^99mTc-(V)DMSA is a credible non-invasive proliferation depicter, its cellular accumulation linked closely to phosphate uptake and kinase pathway activation. A potential role in patient management, prognosis estimation, and therapy response monitoring could occur for this tracer.     

A strategy for selective anti-cancer drug concentration increase in rat glioma tissue with Ca2+-channel blocker co-administration: calcium kinetics in intra-glioma arteriolar smooth muscle cells

Summary A rat glioma model was employed to estimate the Ca²⁺ kinetics in the tumor arteriolar smooth muscle cells. Electron microcytochemistry revealed that the density of intracellular Ca²⁺ deposits in the intra-tumor arteriolar smooth muscle cells was significantly greater, with slightly higher membrane Ca²⁺-adenosine triphosphatase (ATPase) activity, compared to the contralateral cerebral arterioles. Furthermore, the administration of tyrphostin, a tyrosine kinase inhibitor, specifically increased only the intra-tumor blood flow. These findings suggest that the condition of the intra-tumor arteriole alters the susceptibility to contraction by the accelerated Ca²⁺ influx into the cytoplasm mediated through the tyrosine kinase pathway. After the administration of diltiazem, which also has a blocking effect on the Ca²⁺-channel mediated through this pathway, the local intra-tumor blood flow showed an increase of 39% with a marked decrease of intracellular Ca²⁺ concentration of the arteriolar smooth muscle cells in the tumor, while the blood flow in the basal ganglia increased by only 8%. The intra-tumor concentration of Nimustine-HCI (ACNU) with co-administration of diltiazem was significantly increased compared to that without the co-administration. Co-administration of diltiazem may be a valuable strategy in chemotherapy for glioma in affording the selective increase of intra-tumor concentration of the anti-cancer drug.     

Successful management of a non-Hodgkin’s lymphoma of the gallbladder by chemotherapy: a case report

Introduction

Non-Hodgkin’s lymphoma of the gallbladder is a rare location of lymphoma.

Case presentation

We report a case of T cell non-Hodgkin’s lymphoma (NHL) of the gallbladder in a 39-year-old man in whom cholecystectomy made the diagnosis. Abdominal ultrasound did not reveal gallbladder stones. At this time, our patient had no lymph nodes. Histopathology of gastric and pulmonary biopsy and cholecystectomy made a definite diagnosis of non-Hodgkin’s T cell lymphoma. Our patient had eight cycles of chemotherapy CHOP 21 (cyclophosphamide 750 mg/m² intravenously (IV) on day 1, doxorubicine 50 mg IV on day 1, vincristine 1.4 mg/m² IV on day 1, and prednisone 40 mg/m² per day from day 1 to day 5 per os) with good response. He was free of disease 12 months after completion of chemotherapy. Gallbladder location of NHL is rare and has to be suspected every time when lymph nodes are associated, and we postulate that delays in making the diagnosis may lead to underdiagnosis of lymphoma of the gallbladder.

Conclusion

Review of the literature shows the existence of non-Hodgkin’s lymphoma of the gallbladder, its rarity, and its general dismal prognosis. Our case illustrated that the prognosis could be improved by correct chemotherapy.