Electron irradiation of conjunctival lymphoma--Monte Carlo simulation of the minute dose distribution and technique optimization.

PURPOSE: External beam radiotherapy is the only conservative curative approach for Stage I non-Hodgkin lymphomas of the conjunctiva. The target volume is geometrically complex because it includes the eyeball and lid conjunctiva. Furthermore, the target volume is adjacent to radiosensitive structures, including the lens, lacrimal glands, cornea, retina, and papilla. The radiotherapy planning and optimization requires accurate calculation of the dose in these anatomical structures that are much smaller than the structures traditionally considered in radiotherapy. Neither conventional treatment planning systems nor dosimetric measurements can reliably determine the dose distribution in these small irradiated volumes. METHODS AND MATERIALS: The Monte Carlo simulations of a Varian Clinac 2100 C/D and human eye were performed using the penelope and penEasyLinac codes. Dose distributions and dose volume histograms were calculated for the bulbar conjunctiva, cornea, lens, retina, papilla, lacrimal gland, and anterior and posterior hemispheres. RESULTS: The simulated results allow choosing the most adequate treatment setup configuration, which is an electron beam energy of 6 MeV with additional bolus and collimation by a cerrobend block with a central cylindrical hole of 3.0 cm diameter and central cylindrical rod of 1.0 cm diameter. CONCLUSIONS: Monte Carlo simulation is a useful method to calculate the minute dose distribution in ocular tissue and to optimize the electron irradiation technique in highly critical structures. Using a voxelized eye phantom based on patient computed tomography images, the dose distribution can be estimated with a standard statistical uncertainty of less than 2.4% in 3 min using a computing cluster with 30 cores, which makes this planning technique clinically relevant.

Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy.

BACKGROUND: Currently, objective tests are lacking that enable the extent and duration of intestinal mucosal damage induced by myeloablative chemotherapy to be determined. To address this problem, we explored a citrulline-based assessment score as this amino acid is a simple quantitative marker of intestinal failure. PATIENTS AND METHODS: From March 2004 to June 2007, citrulline concentrations were determined at baseline and at least once weekly after the start of myeloablative chemotherapy until 30 days thereafter among 94 allogeneic or autologous haematopoietic stem-cell transplant recipients. The patients were divided into three groups according to the regimen they received: (i) carmustine, etoposide, cytarabine and melphalan/high-dose melphalan, (ii) cyclophosphamide and total body irradiation +/- antithymocyte globulin and (iii) idarubicin-containing regimens. Intestinal mucosal damage was described either by level of citrulline on each day, on the basis of different thresholds of citrulline indicating the severity of villous atrophy, or by area under the curve using reciprocal value of 10/citrulline. RESULTS: Regimens that incorporated idarubicin induced the most severe intestinal toxicity. Scores based on the level of citrulline, using severity thresholds, and on the area under the reciprocal curve are able to discriminate between the damage induced by different high-dose chemotherapy regimens. CONCLUSION: A citrulline-based assessment score appears objective, validated, reproducible, reliable, specific and sensitive making it a suitable first choice for measuring and monitoring intestinal mucositis.

Correlation of pretransplant and early post-transplant response assessment with outcomes after reduced-intensity allogeneic hematopoietic stem cell transplantation for non-Hodgkin's lymphoma.

BACKGROUND: Chemotherapy sensitivity, defined simply as at least a partial response to chemotherapy, is an important outcome predictor for non-Hodgkin lymphoma (NHL) patients undergoing reduced-intensity allogeneic hematopoietic stem cell transplantation (allo-HCT). The authors hypothesized that further differentiation of chemotherapy sensitivity by specific response, complete remission (CR) versus partial remission (PR) versus stable disease (SD) versus progression of disease (PD), correlates with post-transplant outcomes. METHODS: The impact of pretransplant and early (28 days) post-transplant disease response on transplant outcomes was analyzed in 63 NHL patients treated with reduced-intensity allo-HCT. RESULTS: The 3-year event-free survival (EFS) and overall survival (OS) (median potential follow-up after reduced-intensity allo-HCT = 58 months) for all patients was 37% and 47%, respectively. The 3-year EFS based on pretransplant response was: CR = 50%; PR = 66%; SD = 18%; no patient with PD pretransplant reached 3-year follow-up. The 3-year OS based on pretransplant response was: CR = 63%; PR = 69%; SD = 45%. The 3-year EFS based on post-transplant response was: CR = 57%; PR = 32%; SD = 33%; no patient with PD post-transplant reached 3-year follow-up. The 3-year OS based on post-transplant response was: CR = 65%; PR = 43%; SD = 50%. In multivariate analyses, pretransplant response was the best predictor of EFS (P < .0001). Pretransplant response (P < .0001) and age (P = .0035) were jointly associated with OS. CONCLUSIONS: These data suggest that NHL patients with pretransplant SD, generally considered inappropriate candidates, may benefit from reduced-intensity allo-HCT, and patients with pretransplant PD should only receive this therapy in clinical trials.

Management of poor peripheral blood stem cell mobilization: incidence, predictive factors, alternative strategies and outcome. A retrospective analysis on 2177 patients from three major Italian institutions.

CD34+ peripheral blood hematopoietic stem cells (HSC) are usually collected following mobilization therapy accomplished by using growth factors (GF) such as rHuG-CSF or rHuGM-CSF with or without chemotherapy. A target dose of yielded CD34+ is usually prescribed by the attending physician depending on different protocols, which may include single or double transplantation. HSC collection usually is performed when at least 20 CD34+ HSC/microL are detected by means of flow cytometry. A cumulative dose of at least 2 x 10(6)/Kg/bw CD34+ HSC has been considered as the threshold to allow a prompt and persistent hematopoietic recovery. Unfortunately, this goal is not achieved by the totality of patients undergoing mobilization regimen. In fact, 5-46% of patients who underwent mobilization therapy fail HSC collection due to very low peripheral blood HSC CD34+ count. Patients' characteristics, including age, sex, stage of the underlying disease (complete or partial remission), diagnosis, previously administered radio/chemotherapy regimens, time-lapse from last chemotherapy before mobilization and mobilization schedule (including dose of GF) were considered as possibly predictive of poor or failed mobilization. We performed a retrospective analysis in 2177 patients from three large Italian academic institutions to assess the incidence of poor mobilizers within our patients' series. Therefore, a patient who fails a first mobilization (and when an HLA-compatible related on unrelated donor is not available) could undergo a second attempt either with different mobilization schedule or by using different GF, such as stem cell factor, growth hormone (GH), or more recently newly introduced drugs such as AMD3100, alone or in combination with rHuG- or -rHuGM-CSF. Thus, we investigated the fate of those who failed a first mobilization and subsequently underwent a second attempt or alternative therapeutic approaches.

Individual physician practice variation in hematopoietic cell transplantation.

PURPOSE: Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. METHODS: An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. RESULTS: Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. CONCLUSION: These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.

Overview of early response assessment in lymphoma with FDG-PET.

Early assessment of response to chemotherapy with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is becoming a routine part of management in patients with Hodgkin lymphoma (HL) and histologically aggressive non-Hodgkin lymphoma (NHL). Changes in FDG uptake can occur soon after the initiation of therapy and they precede changes in tumour volume. Recent studies in uniform populations of aggressive lymphomas (predominantly diffuse large B cell lymphomas) and HL have clarified the value of early response assessment with PET. These trials show that PET imaging after 2-3 chemotherapy cycles is far superior to CT-based imaging in predicting progression-free survival and can be at least as reliable as definitive response assessment at the end of therapy. This information is of great potential value to patients, but oncologists should be cautious in the use of early PET response in determining choice of therapy until some critical questions are answered. These include: When is the best time to use PET for response assessment? What is the best methodology, visual or quantitative? (For HL at least, visual reading appears superior to an SUV-based assessment). Can early responders be cured with less intensive therapy? Will survival be better for patients treated more intensively because they have a poor interim metabolic response? In the future, early PET will be crucial in developing response-adapted therapy but without further carefully designed clinical trials, oncologists will remain uncertain how best to use this new information.

[Role of surgery in the treatment of primary gastric lymphoma and assessment of new therapeutic approaches]. / Il ruolo della chirurgia nel trattamento dei linfomi gastrici primitivi e valutazione dei nuovi orientamenti terapeutici.

Controversy remains regarding the best treatment for primary gastric lymphoma (PGL). Recent developments in diagnosis and chemotherapy have changed strategies for this disease. Fourteen patients with primary gastric non-Hodgkin's lymphoma underwent surgery. Before surgery 9/14 patients underwent Helicobacter pylori eradication, and 4/14 were treated with chemotherapy. In two patients chemotherapy was not possible because of risk of perforation recurred. Total gastrectomy with N2 lymphadenectomy, splenectomy, biopsy of mesenteric lymph nodes, and hepatic biopsy were done. Then patients underwent post-operative chemotherapy. Involved-field radiation therapy was made in four patients. The overall survival was 64.2 percent. Surgery was the treatment of choice in cases of gastric lymphoma non-responsive to medical therapy and to control complications or when gastroscopy did not supply correct diagnosis.

Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study.

The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166; Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate) regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony-stimulating factor-mobilized stem cells after the second DHAP course or autologous bone marrow cells before the second DHAP course. These stem cells were reinfused following high-dose myeloblative chemotherapy. After induction, 118 patients obtained a partial or complete response and were eligible for randomization. In the PSCT arm (n = 76) significantly faster engraftment of neutrophils [> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range), 15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01] and thrombocytes [> or = 20 x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01] were observed. In addition, significantly fewer transfusions of red blood cells [6 (0-23) versus 8 (2-24), P < 0.01] and platelets [4 (0-60) versus 8 (2-55), P = 0.01] were required in the PSCT arm. These findings were associated with a significant reduction in the median days of intravenous antibiotics in patients with fever [8.5 (0-30) versus 14 (0-34), P = 0.04] and hospital stay [27 (8-51) versus 34 (24-78), P < 0.05]. Quality of life demonstrated a significant difference in favour of the PSCT arm. Total transplantation costs were significantly lower in the PSCT arm [$13,954 ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05], as a result of the reduced hospital stay and lower antibiotic costs. In summary, these results indicate that PSCT is superior to ABMT with regard to engraftment, supportive care, quality of life and cost.

Assessment of intracardiac masses by transesophageal echocardiography.

Transesophageal echocardiography and 2-dimensional transthoracic echocardiography have proved to be extremely valuable in the diagnosis of cardiac masses. In this report, we review the echocardiographic findings, clinical history, and histopathologic findings in 21 patients with intracardiac masses who underwent transthoracic echocardiography, transesophageal echocardiography, or both, at our institution. Of these patients, 14 had benign masses and 7 had malignant tumors. The potential role of transesophageal echocardiography in the diagnosis and treatment of patients with intracardiac masses is discussed. We believe that transesophageal echocardiography offers the cardiologist and cardiovascular surgeon the capability of more accurate preoperative and intraoperative assessment of cardiac masses.

Dynamic assessment of quality of life after autologous bone marrow transplantation.

To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy-eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient.

Magnetic resonance imaging--a useful tool for airway assessment.

The case is presented of a 58-year old man with a malignant non-Hodgkin's lymphoma of the root of the tongue. Preoperative magnetic resonance imaging (MRI) proved extremely useful in the evaluation of the upper aerodigestive tract, by providing sagittal sections of the hypopharynx and the inlet of the larynx. Thus, a potentially difficult intubation was confirmed in a patient in whom other investigations would not have produced comparable conclusions. Difficulties in airway management were avoided by performing a tracheostomy under local anesthesia. This represents a novel application of MRI, which might contribute to the safety of airway management.