Does Rituximab Have a Place in Treating Classic Hodgkin Lymphoma?

Monoclonal antibodies targeting surface proteins on the malignant Hodgkin and Reed-Sternberg (HRS) cells are currently under intensive investigation with promising early results. Of particular interest is the CD20 antigen, because it is expressed not only on a small fraction of HRS cells but also on the benign reactive B cells in the microenvironment. The rationale of using rituximab in classic Hodgkin lymphoma (cHL) comprises several points: 1) HRS cells infrequently express CD20; 2) elimination of CD20-positive reactive B cells supporting HRS cells would deprive the malignant cells of survival signals; 3) elimination of reactive B cells may also potentially increase host immune response against HRS cells; 4) HRS stem cells express CD20. Although this rationale has not generally been confirmed in patients, promising results in managing cHL have occurred in early-phase clinical trials of rituximab, including trials of rituximab as a single agent in refractory or recurrent cHL, rituximab plus gemcitabine in refractory or recurrent cHL, and rituximab plus ABVD in newly diagnosed cHL. Based on the results of these trials, several prospective clinical trials using rituximab in the management of advanced-stage cHL and early-stage cHL are ongoing. These trials further clarify the role of rituximab in cHL. Enrollment of patients with this “classic” disease in clinical trials is encouraged.     

Mortality is persistently increased in Hodgkin’s lymphoma survivors

BackgroundNegative health outcomes of chronic fatigue (CF) in disease-free cancer survivors are mainly unexplored. Aims of this study were to examine mortality and causes of death in Hodgkin’s lymphoma survivors (HLSs) compared to controls from the general population, and to explore if CF was associated with increased mortality.MethodsHLSs (n = 557) invited to participate in a survey on late effects in 1994 were divided into three groups: participants without CF (n = 329), participants with CF (n = 113), non-participants (n = 98). Controls matched for gender and age were drawn from the general population (five per HLSs, n = 2785). Observation time was calculated from 1st January 1994 until date of death or cut-off at 1st January 2007. Kaplan–Meier plots were used for univariate analyses and Cox models for multiple covariates.ResultsCompared to controls HLSs had nearly five times higher mortality (HR = 4.93; 95% confidence interval [CI]: 3.91–6.21) and the mortality rate of HLSs was higher than the rate of their controls for the entire observation period. Mortality was increased in all groups: participants with CF: HR = 4.85 (95% CI: 3.02–7.77), participants without CF: HR = 4.35 (95% CI: 3.16–6.00), non-participants: HR = 9.45 (95% CI: 5.44–16.41).Compared to the controls HLSs had over six times increased mortality of cancer (HR: 6.6, 95% CI: 4.7–9.2) and almost five times increased mortality of cardiovascular diseases (HR: 4.9, 95% CI: 3.1–7.9).ConclusionsHLSs had almost five-time increased mortality compared to controls. CF was not associated with increased mortality rate. The high mortality among the non-participating HLSs indicates that serious health problems are underestimated in this group. This has implications for the interpretation of surveys in cancer survivors.     

PET-directed therapy in Hodgkin lymphoma: Ready for prime time?

Advances in chemotherapy and radiation therapy have allowed the vast majority of patients with Hodgkin lymphoma to be cured, but some of these patients develop treatment-related complications, including second malignancies, cardiovascular disease, and thyroid disease. Efforts to decrease exposure of patients to more chemotherapy or radiation therapy than is necessary to cure their disease have led to a trend toward shortened treatment regimens in patients with low-risk disease. Predicting which patients will relapse, and therefore might benefit from a more intense treatment regimen, has been a clinical challenge. PET has emerged as a useful modality in the diagnosis and management of Hodgkin lymphoma, and has been studied as a potential tool to help the oncologist to utilize the optimal chemotherapy and radiation therapy regimen for each patient.     

Double‐hit lymphoma: So what?

The revised WHO classification moved all aggressive B‐cell lymphomas with a MYC translocation and a concurrent translocation of BCL2 and/or BCL6 into a single diagnostic category. These are the double‐ and triple‐hit lymphomas. These represent a group with typically a poor outcome to conventional therapy, and as a result, intensification of immunochemotherapy has been explored. The optimal approach is far from clear, and recent insight into the biology suggest that they may represent just a subgroup of molecular high‐grade B‐cell lymphomas that maybe identified by gene expression profiling. There are a number of novel therapeutic approaches under investigation.     

What is new in lymphoma?

The lymphomas are a diverse group of malignant disorders that vary with respect to their molecular features, genetics, clinical presentation, treatment approaches, and outcome. Over the past few years, there have been major advances in our understanding of the biology of these diseases, leading to a universally adopted World Health Organization classification system. New therapies are now available with the potential to improve patient outcome, and the International Prognostic Index and standardized response criteria help make clinical trials interpretable. Most notably, the chimeric antiCD20 monoclonal antibody rituximab has altered our therapeutic paradigms for B-cell disorders. Combinations of this antibody with chemotherapy and other biologic agents have shown promise in treating lymphoma. Other antibodies, radioimmunoconjugates (such as Y-90 ibritumomab tiuxetan and I-131 tositumomab), and oblimerson sodium (a BCL-2 antisense oligonucleotide) have all shown promise. New chemotherapy regimens such as bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), agents such as gemcitabine, and monoclonal antibodies directed against CD30 are also being studied in Hodgkin Lymphoma. The challenge of clinical research is to optimize the use of these agents, select patients most likely to respond, and develop multitargeted strategies based on sound scientific rational, with the potential to increase the cure rate of patients with lymphomas.     

Intensity modulated radiotherapy for intrathoracic cancers: a dangerous liaison? Our experience in the treatment of Hodgkin lymphoma mediastinal masses

IMRT is a seducing treatment option in patients with Hodgkin lymphoma mediastinal masses due to the complex form of the tumour masses and their proximity to organs at risk such as the heart and the coronary arteries. This treatment delivery technique remains risky owing to respiratory movements and heart beats. The concomitant use of IMRT and respiratory gating is enticing, but a number of theoretical and practical hurdles remain to be resolved before it can be used in clinical daily practice.     

Childhood Hodgkin lymphoma in Casablanca, Morocco: 24 years’ experience in a single institution

Background

More than 90% of children with Hodgkin lymphoma (HL) can be cured with current treatment modalities. This goal has not, however, been reached in most developing countries. We report here the results of a retrospective study of 24 years’ experience in the management of HL in children in one institution in Morocco.

Procedure

All cases of histologically confirmed HL in children under 17 years of age seen in our department between 1978 and 2001 were included in this study. The treatment modality varied during the 24-year period but mainly comprised combined chemotherapy and radiation therapy.

Results

Two hundred and three patients were included. The mean age of the patients was 10.3 years, and 46% were 10 years old or less. The male:female ratio was 2.9. The mean duration of symptoms before diagnosis was 10.4 months. Lukes-Rye histological types 2 and 3 predominated, representing 40% and 37% of cases, respectively. Advanced stages III and IV represented 55.5% of the cases. After a median follow-up of 10 years, only 134 patients were available for evaluation. The 10-year overall and relapse-free survival rates were 64% and 58%, respectively.

Conclusion

The results for this large series of cases of childhood HL in Morocco are similar to those observed in other developing countries. Steps must be taken, however, to reduce the numbers who abandon treatment and to improve the therapeutic results.     

Can supine breast magnetic resonance imaging help hit the target in extreme oncoplastic surgery?

ObjectivesTo evaluate the clinical value of supine magnetic resonance imaging (MRI) for tumor localization in breast cancer patients with large or multifocal tumors detected by prone MRI, scheduled for oncoplastic breast conserving surgery (OBCS). Outcomes were compared with those of patients who underwent wide local excision (WLE) or OBCS without MRI guidance.MethodsOver a 2-year period, consecutive patients with large or multifocal disease scheduled for OBCS with MRI-only findings were invited to participate (Group-1). Supplementary supine MRI was performed, and tumor margins were marked in the surgical position. Consecutive patients with early, non-palpable breast cancer who underwent WLE (Group-2) or OBCS (Group-3) were included for comparisons. The primary outcome was reoperation due to an insufficient margin. Secondary outcomes included surgical complications and delayed adjuvant treatment.ResultsAltogether, 102 breasts (98 patients) were analyzed. All preoperative demographic data were comparable among the three groups. Multifocality, tumor-to-breast volume ratio, and the volume of excised breast tissue were significantly greater in Group-1 than in Groups-2 and 3. Operation time was longer and the need for axillary clearance or surgery for both breasts was more common in Groups-1 and 3 than in Group-2. Adequate margins were achieved in all patients in Groups-1 and 2, and one patient underwent re-excision in Group-3.ConclusionsSupine MRI in the surgical position is a new, promising method to localize multifocal, large tumors visible on MRI. Its short-term outcomes were comparable with those of conventional WLE and OBCS.