Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this ...technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms.
The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account.
The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.
•A fast GPU based MC has been developed for IOeRT breast treatment planning.•The input is an ultrasound image with defined PTV and OARs.•Different applicator positions, dimensions and angles and beam energies are tested.•Plan is optimised using absorbed dose maps and related DVHs.•Results in the context of conventional and FLASH irradiations are discussed.
Acute promyelocytic leukemia (APL) is typified by the t(15;17) translocation, which leads to the formation of the PML/RARA fusion gene and predicts a beneficial response to retinoids. However, ...approximately 10% of all APL cases lack the classic t(15;17). This group includes (1) cases with cryptic PML/RARA gene rearrangements and t(5;17) that leads to the NPM/RARA fusion gene, which are retinoid-responsive, and (2) cases with t(11;17)(q23;q21) that are associated with the PLZF/RARA fusion gene, which are retinoid-resistant. A key issue is how to rapidly distinguish subtypes of APL that demand distinct treatment approaches. To address this issue, a European workshop was held in Monza, Italy, during June 1997, and a morphologic, immunophenotypic, cytogenetic, and molecular review was undertaken in 60 cases of APL lacking t(15;17). This process led to the development of a novel morphologic classification system that takes into account the major nuclear and cytoplasmic features of APL. There were no major differences observed in morphology or immunophenotype between cases with the classic t(15;17) and those with the cryptic PML/RARA gene rearrangements. Auer rods were absent in the t(5;17) case expressing NPM/RARA. Interestingly, this classification system distinguished 9 cases with t(11;17)(q23;q21) and, in addition, successfully identified 2 cases lacking t(11;17), which were subsequently shown to have underlying PLZF/RARA fusions. The PLZF/RARA cases were characterized by a predominance of blasts with regular nuclei, an increased number of Pelger-like cells, and by expression of CD56 in 4 of 6 cases tested. Use of this classification system, combined with an analysis for CD56 expression, should allow early recognition of APL cases requiring tailored molecular investigations. (Blood. 2000;96:1287-1296)
In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell ...non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.
Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute ...promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy.
Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis.
Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56(+). No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56(+) and CD56(-) populations. Conversely, compared with patients who were CD56(-), patients with CD56(+) APL had shorter CR duration (P =.04) and overall survival (P =.002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 x 10(9) cells/L retained statistical significance in overall survival (P =.04 and P =.02, respectively).
The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.
High-dose chemotherapy and autologous stem cell transplantation play an important role in achieving long-term remission in certain groups of patients with non-Hodgkin's lymphoma. A potential ...advantage of using mobilized peripheral blood stem cells (PBSC) is the possibility of harvesting a great number of hematopoietic stem cells capable of more rapid engraftment. The DHAP regimen was thus integrated into various treatment plans tailored for NHL patients as a salvage chemotherapy and mobilizing regimen. A a single injection of pegfilgrastim has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, whereas the experiences with pegfilgrastim in mobilization of PBSC are limited. The study included 72 patients with NHL (42 follicular and 30 large cells). The mean age was 37 years (range 17-60). Sixty-four patients (88.9%) had stage III-IV disease. Forty-eight patients (66.7%) had bone marrow involvement. Mobilization chemotherapy regimens were DHAP plus filgrastim in 38 patients (52.7%) or pegfilgrastim in 34 (47.2%). Pegfilgrastim 6 mg was given subcutaneously on days +6; filgrastim 5 microg/ kg/days from day +6. Sixty-five out of 72 patients harvested a median of 12.3 x 10.sup.6/CD34+ cells (range 2.5-28.9) after a median of 13 days (range 8-16 days), with a single apheresis procedure in 58 (80.6%) cases. Failure to mobilize, defined as failure to reach a circulating CD34+ cell count of 10/mcl, occurred in 5 patients (13.2%) in the Filgrastim group and 8 (23.5%) in the pegfilgrastim group (p = ns). The mean number of CD34+ cells collected was 13.2 x 10e6/kg in the pegfilgrastim group and 12.3 x 10.sup.6/kg in the filgrastim group (p = ns). A median of CD34+ >10 cells/ microl in peripheral blood was reached in 12 days (range 8-14) in filgrastim group and in 15 days (range 12-18) in pegfilgrastim group (p = n.s.). The median duration of CD34+ >10 cells/microl in peripheral blood was 4 days (1-5) in filgrastim group and 7 days (3-12) in pegfilgrastim group (p<0,05). To date, 65 patients have been autografted with a median of 5.4 x 10.sup.6 CD34+ cells/kg (range 2.5-12.9) with no difference in engrafment speed between two groups. The results confirm the efficacy and feasibility of PBSC mobilization with chemotherapy and single-dose pegfilgrastim in patients with non Hodgkin lymphomas. Six mg of pegfilgrastim after chemotherapy induced an adequate mobilization, whereas dose and schedule in heavily pretreated patients need further investigation.
Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative ...Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin Hb less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.
Twenty-five patients (22 adults and 3 infants) with ALL1/AF4-positive acute lymphoblastic leukemia (ALL) were prospectively monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) ...between January 1992 and July 1999. After high-dose induction and consolidation chemotherapy without bone marrow transplantation, all patients had a complete hematologic remission. Using nested RT-PCR (sensitivity 10(-4)), we observed conversion to PCR negativity in 11 (44%) of the patients. Thirteen of the 14 patients who did not have a molecular remission had a relapse at a median time of 4 months (range, 1 - 20 months). Of the 11 patients who had a conversion to PCR negativity, 5 reconverted to PCR positivity within 1 to 14 months. These 5 patients all progressed to hematologic relapse after 2, 3, 4, 4, and 7 months, respectively. Of the remaining 6 patients, 4 are in persistent hematologic and molecular remission at 12, 14, 88, and 96 months, whereas 2 are early in their follow-up. Actuarial probabilities of relapse and overall survival were 100% and 0% at 14 and 24 months and 67% and 43% at 96 and 100 months, respectively, in patients who had persistent RT-PCR positivity and in those who had a molecular remission. For both relapse and survival, the differences observed between the two groups were significant (P =.003 and P <.005, respectively). This study, which represents the first prospective analysis of residual-disease monitoring carried out in a substantial series of patients with t(4;11)-positive ALL, emphasizes the clinical relevance of RT-PCR-based methods to monitor minimal residual disease in this leukemia subset. (Blood. 2000;95:96-101)
