Lavinia Grapulin

MACOP-B and Involved-Field Radiotherapy Is an Effective and Safe Therapy for Primary Mediastinal Large B Cell Lymphoma

PURPOSE To report the clinical findings and long-term results of front-line, third-generation MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) chemotherapy and mediastinal involved-field radiotherapy (IFRT) in 85 consecutive, previously untreated patients with primary mediastinal large B cell lymphoma (PMLBCL) diagnosed and managed at a single institution. METHODS AND MATERIALS Between 1991 and April 2004, 92 consecutive, untreated patients with PMLBCL were treated at our institution. The median age was 33 years (range, 15-61 years), 46 patients (50%) showed a mediastinal syndrome at onset; 52 patients (57%) showed a low/low-intermediate (0 to 1) and 40 patients (43%) an intermediate-high/high (2 to 3) International Prognostic Index (IPI) score. Eighty-five patients were treated with standard chemotherapy (MACOP-B), and 80 underwent mediastinal IFRT at a dose of 30-36 Gy. RESULTS After a MACOP-B regimen, the overall response rate was 87% and the partial response rate 9%. After chemotherapy, (67)Ga scintigraphy/positron emission tomography results were positive in 43 of 52 patients (83%), whereas after IFRT 11 of 52 patients (21%) remained positive (p < 0.0001). After a median follow-up of 81 months (range, 2-196 months), progression or relapse was observed in 15 of 84 patients (18%). The projected 5-year overall survival and progression-free survival rates were 87% and 81%, respectively. The 5-year overall survival and progression-free survival rates were better for patients with an IPI of 0 to 1 than for those with an IPI of 2 to 3 (96% vs. 73% [p = 0.002] and 90% vs. 67% [p = 0.007], respectively). CONCLUSIONS Combined-modality treatment with intensive chemotherapy plus mediastinal IFRT induces high response and lymphoma-free survival rates. Involved-field RT plays an important role in inducing negative results on (67)Ga scintigraphy/positron emission tomography in patients responsive to chemotherapy.

Efficacy of the BEACOPP regimen in refractory and relapsed Hodgkin lymphoma.

The BEACOPP regimen is a consolidated first-line treatment regimen for advanced stage Hodgkin lymphoma (HL), while few data are available on the efficacy of this regimen in advanced disease. About 50% of patients with HL relapsed after or refractory to first-line therapy achieve a durable response after peripheral blood stem cell transplantation (PBSCT). Patients relapsing after a PBSCT (performed as second line therapy) have a very poor prognosis. We evaluated the efficacy of BEACOPP in two settings: patients refractory or in relapse after first-line therapy (Group A) and patients relapsing after a PBSCT (Group B). Twenty-three patients with HL, admitted between February 2003 and April 2007, were retrospectively studied: 10 patients in Group A and 13 in Group B. Group A: Nine complete remissions (CR) and one partial remission (PR) were achieved following BEACOPP treatment. After a median follow-up of 32 months, one patient has died due to secondary leukemia, while the other eight are alive, five (50%) in second CR, three in third CR after PBSCT and one with disease. Group B: Eight of the 13 patients (62%) obtained a CR, one patient a PR, two were refractory and two have died of toxicity. To date, eight patients (62%) are alive, four (31%) still in CR. All patients experienced hematologic toxicity (WHO 3–4) with two deaths due to septic shock. These results show that BEACOPP is an effective regimen for both refractory/relapsed patients with HL after first-line treatment (Group A) and for patients relapsing after a PBSCT (Group B) with a 3-year probability of overall survival, progression-free survival, and cumulative incidence of relapse of 90, 50, and 33.3% in Group A, and 61, 31, and 37.5% in Group B, respectively.

Feasibility and results of a multimodality approach in elderly patients with localized intermediate to high-grade non-Hodgkin's lymphomas.

Aims and background A prospective clinical study to determine efficacy and feasibility of a brief course or standard course of anthracycline-based chemotherapy and consolidation radiation therapy in non-Hodgkins lymphoma patients over 60 years of age. Methods Twenty-five consecutive patients with stage I-IE intermediate to high-grade non-Hodgkins lymphoma aged 60 and older were treated in an outpatient setting in the Radiotherapy Oncology and Hematology units. All patients had a performance status of 0-1 according to WHO criteria. The survival end points, ie, overall survival, disease-free survival and event-free survival, were considered. Lactate dehydrogenase value, nodal versus extranodal localization and dose intensity were assessed as risk factors for disease-free and overall survival. A comparison using logrank analysis with a wellmatched group of stage I-IE non-Hodgkins lymphoma patients aged less than 60 years was performed. Results The 5-year overall and disease-free survival rates were 90% and 86%, respectively. There was no statistical difference with respect to the younger population regarding these survival end points. Finally, the 5-year event-free survival was 85% and 86% for elderly and younger patients, respectively, without statistical difference (P = 0.41). Neither acute nor late toxicity (G3-G4) was observed during chemotherapy and radiotherapy treatment and the follow-up in the elderly group. Conclusions We confirm the efficacy and feasibility of a full-dose combined chemoradiotherapy in elderly patients with a good performance status with localized I-IE intermediate to high-grade non-Hodgkins lymphoma.

Radiotherapy in indolent primary cutaneous B-cell lymphoma

Radiation therapy (RT) remains a powerful single option with curative intention in the local treatment of indolent primary cutaneous B‐cell lymphoma (pcBCL). It is well known that (1) primary cutaneous marginal zone lymphoma (pcMZL) have a much higher relapse rate than primary cutaneous follicle center lymphoma (pcFCL) after RT, (2) pcFCL and pcMZL present at different skin sites, and (3) pcMZL much more often present with multifocal lesions than pcFCL. We presented an analysis of retrospective cohort investigating the role of initial RT in patients with an indolent pcBCL. A radiation dose of 20 to 46 Gy was prescribed. With 131 months (range, 25‐240) follow‐up, we concluded that lesions at other sites than the trunk and the presence of multiple lesions were associated with an increased relapse risk on the basis of a difference in 5‐year relapse‐free survival (RFS) rate for patients with trunk lesion versus those with other location (89.4% versus 66.9%) and in case of single and multiple lesions (83.5% versus 57.1%, P = .04). Several important issues still need to be discussed. First, the multiple lesions definition could be a confounder. We classified multifocal lesions as those lesions requiring different radiation fields. Second, the substantial variation in radiation dose used (20 to 46 Gy) could potentially increase selection bias in this kind of analysis. Indolent pcBCL is a high radioresponsive disease and dose over 30 Gy is unusual, especially in radiosensitive organs such as the eye. With regard to pcBCL, the high total dose up to 46 Gy was prescribed in order to control the disease on a long‐term basis. We have reported excellent clinical outcomes with 10‐year RFS and overall survival rates of 71.1% and 87.1%, respectively. No in‐field recurrences were observed. This high total dose could potentially improve severe late toxicity, including the risk of RT‐induced second malignancies, although dose distribution was just limited to skin zone. We recognize that it could represent an overtreatment, based on current guidelines, but the tumor size at diagnosis could justify 30 to 46 Gy as an appropriate dose, when the intent for treatment was tumor eradication. Surely, this was only one retrospective experience, but we believe it could provide an appropriate tool for a better issues awareness. The use of low‐dose involved‐field RT for indolent pcBCL is generally scheduled in palliative setting. Low doses of 4 Gy have been shown

MINIMAL RESIDUAL DISEASE (MRD) IN EARLY STAGE FOLLICULAR LYMPHOMA CAN PREDICT PROGNOSIS AND DRIVE RITUXIMAB TREATMENT AFTER RADIOTHERAPY

apies in the autoHCT cohort. There was no difference in 5 year OS between the two groups (60% vs 67%, respectively; p = 0.16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5 year OS than those without autoHCT (73% vs 60%, p = 0.02). On multivariate analysis, early use of autoHCT was associated with a significantly reduced risk of mortality (HR = 0.63, 95%CI: 0.42–0.94, p = 0.02). Conclusion: FL patients with ETF after front‐line chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in FL patients experiencing ETF.

Second cancer incidence in primary mediastinal B-cell lymphoma treated with methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin regimen with or without rituximab and mediastinal radiotherapy: Results from a monoinstitutional cohort analysis of long-term survivors

Our aim is to assess the incidence of second cancer in long‐time surviving primary mediastinal B‐cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76‐212), we recorded second cancer in 3 of 80 long‐surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17‐year second cancer‐free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.

An unusual case of fatty liver in a patient with desmoid tumor.

A desmoid tumor, also known as aggressive fibromatosis, is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues. It can occur in any anatomical location, most commonly the abdominal wall, shoulder girdle and retroperitoneum. The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures. It is associated with a high local recurrence rate after resection. Many issues regarding the optimal treatment of desmoid tumors remain controversial. Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life. Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions. Desmoid tumors tend to be locally infiltrative, therefore, the fields must be generous to prevent marginal recurrence. The radiation dose appropriate for treating desmoid tumors remains controversial. We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection, treated with radiotherapy. The patient achieved complete tumor regression at 4 mo after radiotherapy, and he is clinically free of disease at 12 mo after the end of treatment, with an acceptable quality of life. The patient developed short bowel syndrome as a complication of second surgical resection. Consequently, radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.