Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.     

Patient-specific vaccines derived from autologous tumor cell lines as active specific immunotherapy: results of exploratory phase I/II trials in patients with metastatic melanoma

Seventy-four (74) patients with metastatic melanoma were treated with patient-specific vaccines derived from autologous tumor cell lines. Cryopreserved irradiated tumor cells were injected weekly for 3 weeks, then monthly for 5 months. At a median follow up >6 years, the median event-free survival (EFS) was 4.5 months, with 13 patients alive and progression free 6-12 years later. Median overall survival (OS) was 20.5 months, with 29% 5-year OS. Tumor response rate was 9% among the 35 patients with evaluable disease who received at least 3 injections. Better survival was observed for patients who had minimal rather than clinically evident metastatic disease at the time vaccine therapy was initiated (5-yr OS 47% vs. 13%; p < 0.0001), received granulocyte-macrophage colony-stimulating factor and/or interferon gamma as an adjuvant (5-yr EFS 26% vs. 0%; p < 0.0001) or received an average of <7 million cells for each of the first 3 injections, compared to those who received 7-11.9 million or >12 million cells per injection (5-yr EFS OS 35% vs. 24%; p = 0.041 and p = 0.034). There was a trend toward better EFS for those who had a positive delayed type hypersensitivity (DTH) reaction to an intradermal injection of 1 million irradiated tumor cells at baseline, or converted to positive after 3 injections, compared to those whose DTH remained negative (5-yr EFS 39% vs. 18%; p = 0.159). This treatment approach is feasible, produces minimal toxicity, and is associated with longterm survival in a significant proportion of patients.     

Prognostic significance of the ratio of surgically resected to radiologically detected lung nodules in patients with metastatic osteosarcoma

The factors that affect the prognosis of patients’ metastatic osteosarcoma are still poorly understood. In this study, we investigated a new prognostic factor, the ratio of surgically resected to radiologically detected osteosarcoma lung nodules (SR/RD), which may have predictive value.Patients and methodsData from patients with metastatic osteosarcoma who underwent metastasectomy between January 2009 and December 2020, in a single center, were reviewed. The relationships between survival and the SR/RD ratio, timing of lung metastases, number of nodules, laterality, and presence of tumor necrosis at first metastasectomy were investigated.ResultsAmong the 125 metastatic osteosarcoma patients, 80 patients had an SR/RD ratio ≤1. The median duration of follow-up was 72 months, ranging from 6 to 118 months. The five-year overall survival (OS) and postmetastasectomy event-free survival (EFS) for all patients were 36.5% and 18.1%, respectively. The five-year OS of patients with a low SR/RD ratio was 49.6% and that of patients with a high SR/RD ratio was 11.8 (P = 0.001). The two-year postmetastasectomy EFS rates of the high and low ratio groups were 24.1% and 9.4%, respectively (P = 0.001). The SR/RD ratio, number of nodules, and tumor necrosis had significant effects on OS and postmetastasectomy EFS in univariate analysis. A Cox proportional hazard model demonstrated that tumor necrosis and an SR/RD ratio >1 were associated with OS (HR = 1.8 and 2.01) and postmetastasectomy EFS (HR = 1,69 and 1.97).ConclusionsA high SR/RD ratio of greater than 1 and poor tumor necrosis were significantly associated with poor survival among patients with metastatic osteosarcoma who had lung metastasectomy. The high SR/RD ratio may be a surrogate outcome for incomplete metastatic tumor resection.     

Long-term results (12 years) of high-dose therapy in 127 patients with de novo multiple myeloma.

This report describes the long-term outcome of a cohort of 127 de novo multiple myeloma patients treated with at least one course of high-dose therapy (HDT) in a single institution between June 1985 and December 1995, for whom the minimum follow-up duration for survivors is 6 years. The 12-year overall survival (OS) and event-free survival (EFS) rates are 24.9% and 3.1%, respectively, and the median survival and EFS are 49 and 17 months, respectively. Only four patients are alive and disease-free 79, 90, 132 and 153 after the first HDT, respectively. Three of them received a subsequent allogeneic bone marrow transplantation. Three factors significantly influence OS in this series: B2M at diagnosis, age, and the completion of a second HDT. The 10-year survival is 18.9% for the group of patients with B2M level >3 mg/l at diagnosis as compared with 41% for patients with B2M < or =3, with a median survival of 31 months vs 73 (P = 0.01). The 10-year survival is 23.4% for the group of patients aged >55 years as compared with 36.5% for patients aged <55 years, with a median survival of 34.5 months vs 70.5 (P = 0.04). The 10-year survival is 20.4% for the group of patients who did not receive a second HDT as compared with 35.2% for patients who completed a second HDT, with a median survival of 29 months vs 70 (P = 0.02). In this study we show that some patients treated with HDT experience durable remission and prolonged survival. This survival is significantly influenced by age (< or =55 years), B2M at diagnosis (< or =3 mg/l) and by the completion of two cycles of HDT.     

High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe.

PURPOSE: To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years. PATIENTS AND METHODS: One hundred ninety patients between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m(2) intravenous [IV] or melphalan 140 mg/m(2) IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction). RESULTS: Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03). CONCLUSION: With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.     

Critical role of surgery in patients with gastroesophageal carcinoma with a poor prognosis after chemoradiation as defined by positron emission tomography

BACKGROUND:

The prognosis of patients with localized gastroesophageal carcinoma (LGC) can be defined after chemoradiation by the standardized uptake value (SUV) of positron emission tomography (PET). High SUV (HSUV) after chemoradiation portends a poor prognosis. The authors retrospectively examined the role of surgery in patients with HSUV after chemoradiation.

METHODS:

The authors analyzed the postchemoradiation PET scans of 204 LGC patients. One hundred twenty‐nine patients had HSUV. Two postchemoradiation variables were evaluated: SUV and surgery and their association with overall survival (OS) and event‐free survival (EFS). The log‐rank test, multivariate Cox proportional hazards model, and Kaplan‐Meier survival plots were used to assess the association between OS or EFS and the dichotomized SUV (using the median SUV as the cutoff) and surgery.

RESULTS:

The median SUV was 4.6. The OS of the 52 patients who had an SUV above the median and did not undergo surgery (HSUV‐NS) (median OS, 1.22 years; 95% confidence interval [95% CI], 1.02‐2.16 years) was much shorter than that of the 77 patients with an SUV above the median who underwent surgery (HSUV‐S) (median OS, 2.7 years; 95% CI, 2.43 years to not reached [P <.0001]). Similarly, the EFS for patients with HSUV‐NS was significantly shorter than that for patients with HSUV‐S (P = .001). In the multivariate analyses, patients who underwent surgery (irrespective of SUV) had a lower risk of death (P = .0001) and disease progression (P = .002).

CONCLUSIONS:

The data from the current study suggest that surgery may prolong OS and EFS in patients with a poor prognosis after chemoradiation as defined by PET. However, these data need confirmation. Cancer 2010. © 2010 American Cancer Society.     

Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma

OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). Methods: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.     

血清胱抑素C在多发性骨髓瘤预后中的意义

目的 探讨血清胱抑素C（Cys-C）在多发性骨髓瘤（MM）预后中的意义.方法 收集初诊MM患者160例,平均年龄61.38岁,治疗前检测Cys-C、血清肌酐、β2-微球蛋白（β2-MG）、乳酸脱氢酶（LDH）及血红蛋白水平;中位随访38个月,观察Cys-C与总生存（OS）、无事件生存（EFS）的关系.结果 160例MM患者Cys-C水平为（0.96±0.32） mg/L,高于80例健康对照组的（0.71±0.16）mg/L（P＜0.000）;按ISS分期,Ⅰ期患者Cys-C水平为（0.70±0.13）mg/L,Ⅱ期为（0.87±0.16）mg/L,Ⅲ期为（1.23±0.33）mg/L,各期间Cys-C水平差异均有统计学意义（均P＜0.05）;Cys-C与血清肌酐、β2-MG、LDH呈正相关（r=0.669,r=0.672,r=0.521;均P＜ 0.000）,与血红蛋白呈负相关（r=-0.436,P＜ 0.000）.用ROC分析,Cys-C水平＞0.95 mg/L的患者和Cys-C≤0.95 mg/L的患者相比有较短的EFS和OS（中位EFS分别为30、57个月,P＜0.05;中位OS分别为43、68个月,P＜0.05）.结论 对于MM患者,Cys-C不仅是反应肾损害的敏感指标,也是反应肿瘤负荷及判断预后的指标之一.     

Increased bone marrow microvessel density in newly diagnosed multiple myeloma carries a poor prognosis.

Solid organ tumors associated with neoangiogenesis, as measured by increased microvessel density (MVD), have poorer prognoses. A similar observation of increased MVD has been made in hematologic malignancies; however, its prognostic significance remains unknown. We investigated changes in MVD in 122 newly diagnosed multiple myeloma patients uniformly treated according to the "Total Therapy" protocol (remission induction followed by tandem autotransplants and interferon maintenance) from a set of 231 patients. MVD was measured as mean of 10 fields (MVD) and the single highest field (SHF) on anti-CD34-stained Zenker-fixed paraffin-embedded bone marrow biopsy sections at 400x magnification. MVD was markedly elevated in this population, with a median of 4.4 vessels/field (range, 0.6 to 55.7), and SHF was 13 vessels/field (range, 2 to 80). When compared to 54 patients with less than 4 MVD, 67 patients with mean MVD of greater than 4 had a significantly inferior median duration of event-free survival (EFS) (2.7 v 4.3 years; P =.03), overall survival (OS) (4.3 v 7.9+ years, P =.006), and median complete response (CR) duration (2.2 v 6.8+ years, P=.003). A similarly significant unfavorable relationship to EFS and OS was present for SHF greater than 13. On multivariate analysis of other previously recognized prognostic factors (beta(2)-microglobulin [beta2M], C-reactive protein [CRP], and Bartl grade; and deletion 13), MVD < or = 4 emerged as a major favorable prognostic variable for OS followed by CRP < or = 4, P=.006. Thus, tumor-associated angiogenesis as reflected by MVD is a biologically relevant and important prognostic feature that can be targeted by antiangiogenesis therapy such as thalidomide, which has remarkable antitumor activity in advanced and refractory multiple myeloma.     

Cardiovascular toxicity is increased, but manageable, during high-dose chemotherapy and autologous peripheral blood stem cell transplantation for patients aged 60 years and older

High-dose therapy (HDT) for non-Hodgkins lymphoma (NHL) and multiple myeloma (MM) is considered a feasible option for patients aged 60 years. This study compared the outcomes for all patients aged 60 years treated with HDT at the center to a matched cohort group aged <60 years. Results for patients who were 60 years at HDT between 1997--2002 were retrospectively analysed to assess efficacy and safety. Event-free (EFS) and overall survival (OS) rates were compared with a cohort group, matched by disease type, chemotherapy sensitivity, year of treatment and conditioning regimen. Patients with NHL were also matched by International Prognostic Index score. Forty patients aged 60 years were identified. Median age was 65 (range 60--76) with 22 MM and 18 NHL; 50% had 1 or more co-morbidity; 35% had cardiovascular co-morbidity vs. 18% of controls (p=0.075). Response rates (RR) following HDT for MM were: 4 (18%) complete responses (CR) and 18 (82%) partial responses (PR), giving an overall response rate (ORR) of 100%, vs. 77% for controls (p=0.02). For NHL patients there were: 8 CR (44%) and 4 PR (22%), giving an ORR of 67%, vs. 83% for controls (p=0.3). Transplant-related mortality was 8% compared to 5% in controls (p=0.6). Toxicities were similar with the exception of cardiac toxicity, which was significantly higher in patients aged 60 years vs. controls (50% grade 3 vs. 10%: p<0.0001). Atrial fibrillation was the most frequent cardiovascular toxicity (9 patients). At a median follow-up of 33 months, there is no significant difference between older vs. younger patients in median EFS (24 vs. 38 months: p=0.78) or OS (40 months vs. not reached: p=0.23). HDT is feasible and effective in selected patients 60 years with MM and NHL. Patients 60 years are more susceptible to cardiovascular toxicities, particularly atrial fibrillation, but have similar or better response rates following HDT and similar long-term outcomes to younger patients.     

Patients with ERCC1-negative locally advanced esophageal cancers may benefit from preoperative chemoradiotherapy

PURPOSE: To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. EXPERIMENTAL DESIGN: Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. RESULTS: Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score 相似文献   

Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m(2)).

Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m(2), MEL200) vs standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m(2), MEL100) is also superior to the standard dose, but has not been clinically compared with MEL200. A total of 90 patients at diagnosis were treated with two MEL100 courses. Their clinical outcome was compared with that of a control group of 90 pair mates matched for serum beta2-microglobulin levels and Durie and Salmon clinical stage. These patients were treated at diagnosis with two MEL200 courses. Patient characteristics were similar in both groups except that the median age of the MEL100 group was significantly higher (P<0.0001). Complete remission was 35% after MEL100 and 48% after MEL200 (P=0.08). Median event-free survival (EFS) was 32 months in the MEL100 group and 42 months in the MEL200 group (P<0.005), but overall survival (OS) was not different. Transplant-related mortality was not significantly different. Haematological and extra-haematological toxicity was significantly reduced after MEL100. Despite the significant age difference, tandem MEL100 was less toxic than tandem MEL200, and MEL100 was inferior to MEL200 in terms of EFS but not in terms of OS. The intensified nonmyeloablative MEL100 regimen is an effective first-line treatment.     

Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma

Bisphophonates are the treatment of choice to prevent skeletal events in patients with multiple myeloma. Some preclinical studies suggested that bisphophonates can be useful as antitumor drugs in some malignancies. We conducted a controlled clinical trial to assess if zoledronic acid can have this clinical activity. Ninety four patients with previously untreated multiple myeloma were treated with a conventional chemotherapy program: cyclophosphamide, vincristine, melphalan, and prednisone (CVMP) and were randomized to received either zoledronic acid (4 mg, iv, every 28 d) or not (control group). The end-point of the present study was to assess improvement in outcome, measured by event-free survival (EFS) and overall survival (OS), and the second-end point was to confirm the efficacy in preventing skeletal events. In an intent-to-treat analysis, all patients were available for efficacy and toxicity. Median follow up was 49.6 mo (range: 34-72 mo). Five year actuarial curves showed that EFS was 80% in the zoledronic acid group, which was statistically different from 52% in the control group (p < 0.01). Actuarial 5 yr OS was 80% in the zoledronic acid arm, and 46% in the control group (p < 0.01). Sketeletal events were more frequent in the control group when compared to zoledronic acid. Toxicity was mild. We confirm the efficacy of zoledronic acid to prevent skeletal events, but we felt that we can demonstrate that zoledronic acid has a clinical antitumor effect measured from a increase in complete response rate and EFS and OS that were better when compared with the control group. We began a controlled clinical trial with modern treatment (including transplant procedures) in combination with zoledronic acid to define the role of zoledonic acid in this setting of patients.     

Survival improvement of young patients, aged 16-23, with Hodgkin lymphoma (HL) during the last three decades

The prognostic factors, treatments and outcomes of 55 young adults (16-23 years old) with Hodgkin lymphoma (HL) treated in the Second Department of Internal Medicine Propaedeutic, Medical Oncology Unit, Athens University, over the past 25 years, are reviewed. Patients were treated with the chemotherapy regimens available at each time period which were MOPP (Group A; 1978-1987), MOPP/ABVD (Group B; 1988-1993) and BEACOPP or ABVD (Group C; 1994-2003). The eligible patients, received radiotherapy (RT) according to treatment consensus. Additionally, the patients were retrospectively divided according to risk factors (abnormal erythrocyte sedimentation rate (ESR), bulky mediastinal disease, > 3 involved nodes and extranodal involvement) into low [stage I/II; five patients (9%)], intermediate [stage III with adverse prognostic factors; 18 patients (33%)] and high risk categories [stages IIB bulky and III/IV; 32 patients (58%)]. A total of 21 (38%) patients experienced relapse (three intermediate and 19 high risk). The 5-year survival and the 5-year event free survival (EFS) figures were Group A: 65% and 53%, Group B: 80% and 65%, Group C: 100% and 88.5%, respectively, the improvements between Group B and C were statistically significant (p = 0.04 and p = 0.005, respectively) among the three time periods. The overall survival (OS) and EFS differed significantly between intermediate and high risk categories (OS: p = 0.04, EFS: p = 0.005). The sequential use of RT did not influence OS and EFS but there was a trend of improvement with RT in the later periods. Survival of young patients with HL is significantly improving most probably due to improved chemotherapy treatment and understanding of the risk factors. Current controversial issues surrounding this disease, including the role of radiotherapy, positron emission tomography (PET), bone marrow biopsy and stem cell transplantation are discussed.     

Helical Tomotherapy in Head and Neck Cancer: A European Single‐Center Experience

Background.

We report on a retrospective analysis of 147 patients with early and locoregionally advanced squamous cell head and neck cancer (SCCHN) treated with helical tomotherapy (HT).

Patients and Methods.

Included were patients with SCCHN of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), or larynx (L) consecutively treated in one radiotherapy center in 2008 and 2009. The prescribed HT dose was 60–66 Gy in the postoperative setting (group A) and 66–70 Gy when given as primary treatment (group B). HT was given alone, concurrent with systemic therapy (ST), that is, chemotherapy, biotherapy, or both, and with or without induction therapy (IT). Acute and late toxicities are reported using standard criteria; locoregional failure/progression (LRF), distant metastases (DM), and second primary tumors (SPT) were documented, and event-free survival (EFS) and overall survival (OS) were calculated from the start of HT.

Results.

Group A patients received HT alone in 22 cases and HT + ST in 20 cases; group B patients received HT alone in 17 cases and HT + ST in 88 cases. Severe (grade ≥ 3) acute mucosal toxicity and swallowing problems increased with more additional ST. After a median follow-up of 44 months, grade ≥2 late toxicity after HT + ST was approximately twice that of HT alone for skin, subcutis, pharynx, and larynx. Forty percent had grade ≥2 late xerostomia, and 29% had mucosal toxicity. At 3 years, LRF/DM/SPT occurred in 7%/7%/17% and 25%/13%/5% in groups A and B, respectively, leading to a 3-year EFS/OS of 64%/74% and 56%/63% in groups A and B, respectively.

Conclusion.

The use of HT alone or in combination with ST is feasible and promising and has a low late fatality rate. However, late toxicity is nearly twice as high when ST is added to HT.     

Weekly and 3-weekly cisplatin concurrent with intensity-modulated radiotherapy in locally advanced head and neck squamous cell cancer

In loco-regionally advanced head and neck squamous cell cancer (HNSCC), concurrent 3-weekly cisplatin improves overall survival (OS) compared to radiotherapy alone, but is often associated with renal toxicity. The use of radiotherapy with accelerated fractionation schedules has been reported to improve survival but its optimal combination with chemotherapy is unclear. Retrospective analysis of treatment outcome and nephrotoxicity of radiotherapy given with an intensity-modulated approach (IMRT) concurrent with either 3-weekly or weekly cisplatin in 94 patients with stage III/IV HNSCC. Patients treated with weekly cisplatin were significantly older (p=0.0014) and received a significantly lower total cisplatin dose (p=0.0002). With a median follow-up of 2.8 years, at univariate analysis, 3-weekly cisplatin shows a longer OS (p=0.041) but progression-free survival (PFS) is similar for both schedules (p=0.47). Cisplatin doses >240 mg/m(2) were associated with better OS but not PFS. Chronic renal failure rate was significantly higher with 3-weekly cisplatin (p=0.04). Multivariate analysis (Cox regression controlling for age) confirmed the significant and independent impact of alcohol and smoking habits on both PFS (HR, 2.2) and OS (HR, 2.3), while the treatment schedule affected only OS (HR, 2.2). Weekly cisplatin is less nephrotoxic. Both schedules can be combined to curative IMRT. PFS was not significantly different even if patients treated with the weekly schedule were significantly older and received reduced cisplatin doses. The study suggests that the different cisplatin dose doesn't affect the PFS results if concomitant to IMRT. Controlled prospective studies are needed.     

Allogeneic stem-cell transplantation with fludarabine and 2-Gy TBI-based conditioning regimen for chronic hematological malignancy: a study of 25 consecutive patients and a literature review

We analyzed the outcome of 25 consecutive patients with chronic hematological malignancy who underwent allogeneic stem-cell transplantation conditioned with fludarabine (30 mg/m2/day, thrice) and total body irradiation (2 Gy). All patients received peripheral blood stem cells from an HLA-identical sibling donor. With a median follow-up of 769 days (range, 244 - 1231), the estimated 2-year overall survival (OS), event-free survival (EFS), transplantation-related mortality and relapse rates were 53%, 45%, 27%, and 39%, respectively. All patients had initial engraftment. Acute Grade II - IV graft-versus-host disease (GVHD) was recorded in 14 patients (56%), including 7 (28%) with Grade III - IV GVHD. Sixteen of the 23 patients (70%) who survived more than 100 days developed chronic GVHD. OS and EFS were adversely influenced by acute Grade III - IV GVHD (p < 0.001 and p = 0.033, respectively), but chronic GVHD seemed to favorably influence these two parameters (p = 0.03 and p < 0.001, respectively). Patients with full-donor chimerism at day 30 had lower relapse rates, as did those who received high-dose allogeneic CD8+ lymphocytes with their graft (p = 0.026). Collectively, these results provide a framework for refining nonmyeloablative conditioning, to improve outcome with an acceptable risk of GVHD.     

Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1–2 tumor and 1–3 axillary lymph node(s) metastasis

Background

To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1–2 and N1 disease.

Patients and methods.

A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling.

Results

With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI.

Conclusions

For patients with T1–2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.     

CHOP con intensificación de dosis en linfomas no Hodgkin agresivos

Introduction

The aim of this study was to analyse the safety, feasibility, response and survival using dose-intensified CHOP regimen in patients with aggressive non-Hodgkin lymphoma.

Material and methods

Patients (n=26) with a median age of 53 years were treated with CHOP every two weeks and with G-CSF support. Haematologic toxicity grade III/IV neutropenia was 31%. The median follow-up was 20.7 months (range 3–43).

Results

Complete remission was achieved in 16 patients (61%), partial remission in 8 (30.8%), stable disease in 1 (3.8%), and one patient (3.84%) had disease progression. Overall response was obtained in 24 patients (92%). The median event-free survival (EFS) was 12.17 months. The median EFS at two years was 42%. The median overall survival (OS) has not been reached, as yet. After 51 months, the OS was 65%.

Conclusion

This regimen with intensified doses is well tolerated, and the results are better than those achieved with the traditional CHOP with respects to response and OS, but only slightly better in terms of disease-free survival.     

Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?

PURPOSE: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. PATIENTS AND METHODS: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p = NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger (median age 60 vs. 68 years, p <0.001). Severe acute toxicity (ST) was defined as toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU, or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis was used to calculate the actuarial rate of local progression on imaging (LP), the rate of distant metastasis (DM), and the overall survival (OS) rate. The imaging was reviewed in resected patients. RESULTS: Patients receiving gemcitabine developed significantly more ST during treatment (23% vs. 2%, p < 0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1 patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after chemoradiation. Three patients had a short segment (10 cm(2) (p = 0.03) and poor differentiation (p = 0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. CONCLUSION: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose disease met our radiographic definition of unresectable disease had margin-negative resections after treatment with gemcitabine-based chemoradiation. These possible benefits and the high rate of severe toxicity define a very narrow therapeutic index for concurrent gemcitabine-based chemoradiation given by this schedule of administration.