A population-based cohort study on early-stage Hodgkin lymphoma treated with radiotherapy alone: with special reference to older patients.

BACKGROUND: Combined modality treatment has reduced the risk of relapse among younger early-stage Hodgkin lymphoma (HL) patients. Older HL patients may not tolerate chemotherapy and their prognosis is less favorable. We conducted a population-based study to evaluate long-term follow-up outcome in older early-stage HL patients initially treated with radiotherapy (RT) alone. PATIENTS AND METHODS: We included 308 consecutive patients (22% were >or=60 years) diagnosed 1972-1999 (median follow-up 20 years; range 1-28). Using Cox regression models we defined risk of relapse and survival in relation to clinical factors. RESULTS: 272/308 (88%) patients obtained complete remission following first-line RT alone. Among these, 42% relapsed within a median of 21 months. The relapse rate was independent of gender and age at diagnosis (median age 32 years, range 14-85); however, lymphocyte-predominant HL was associated with borderline (P=0.049) 56% decreased risk of relapse. Among patients<60 years and >or=60 years, we observed 29 (median latency 10 years, range 2-25) and 11 (median latency 3 years, range 1-10) second tumors, respectively. CONCLUSIONS: Older age (>or=60 years) was not associated with an increased risk of relapse following RT alone. Given the risks of iatrogenic morbidity/mortality of chemotherapy in older patients, RT alone could be an alternative first-line therapy in early-stage older HL patients.     

Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments.

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.     

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.     

BEACOPP and COPP/ABVD as salvage treatment after primary extended field radiation therapy of early stage Hodgkins disease - results of the German Hodgkin Study Group

Patients with early stage favorable Hodgkin's disease who relapse after extended field radiotherapy have satisfactory results. We retrospectively analysed patients with relapsed HD after initial radiation therapy alone to determine treatment outcome and prognostic factors. Nine-hundred and forty five patients in localized stages without risk factors received either 40 Gy extended field RT or 30 Gy EF RT followed by an additional 10 Gy to involved lymph node regions. 107 patients relapsed and received salvage therapy. Characteristics of the 107 patients at relapse were as follows: median age was 34 years (range 18--75) with relapse occuring at a median of 19 months (range 4--98 months), 31% were female. The majority of patients (93%) were treated with conventional chemotherapy. Sixty-nine percent were treated with COPP/ABVD like regimens, 21% with BEACOPP, and 3% received various other regimens. Seven percent were treated with radiotherapy alone. Complete remission was achieved in 87% of all salvaged patients. The median follow-up after relapse was 45 months. FF2F (freedom from second treatment failure) and OS (overall survival) were 81% and 89%, respectively. In multivariate analysis age was the major prognostic factor for FF2F and OS (p<0.0001, for both). Further independent prognostic factors were B symptoms (p=0.05) and salvage chemotherapy (p=0.03) for FF2F, and B symptoms (p=0.03) and extranodal involvement (p=0.02) for OS. The long-term outcome of patients relapsing after EF RT is excellent. Age, B symptoms, extranodal involvement and salvage chemotherapy were identified as prognostic factors for second relapse and survival.     

Outcomes Related to FDG-PET-CT Response in Patients With Hodgkin Lymphoma Treated With Brentuximab-Vedotin at Relapse or Consolidation

BackgroundBrentuximab-vedotin (BV) monotherapy has shown high efficacy in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL) after high-dose chemotherapy or autologous stem cell transplantation (ASCT). We retrospectively analyzed the outcomes of treatment with BV of HL patients and examined the predictive ability of PET-CT for response in this setting.Patients and methodsRecords of 49 HL patients (median age, 39 years, 55% male) treated with BV for relapse (71.4%) or consolidation (28.6%) post-ASCT were analyzed. Patients who did not reach complete response (CR) on PET/CT after 4 cycles (non-responders) discontinued BV and received the next treatment line. Overall survival (OS) and progression-free survival (PFS) were compared between responders and non-responders.ResultsAfter a median follow-up of 19.1 months, all consolidation patients were alive and none progressed. Median OS in 23 relapsed patients that did not achieve CR after 4 cycles and continued to the next treatment was 55.0 months, while all those in CR (n = 24) were alive (P = .0120). No statistically significant differences in OS were observed between responders and non-responders with relapsed HL (P = .1072). Median PFS evaluated after 4 BV cycles was significantly longer in responders compared to non-responders (47.9 vs. 1.5 months, P < .0001). Neuropathy and neutropenia were the main toxicities observed.ConclusionsHL patients treated with BV for relapse or consolidation who achieved CR by PET-CT after 4 cycles showed improved PFS and OS compared to non-responders. Non-responders treated for relapsed HL who proceeded to the next treatment line demonstrated comparable OS to responders.     

Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract

PURPOSE: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. METHODS AND MATERIALS: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving >or=54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). CONCLUSION: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.     

放疗在早期鼻型NK/T细胞淋巴瘤综合治疗中作用及预后分析

目的 探讨放疗在ⅠE～ⅡE期结外鼻型NK/T细胞淋巴瘤综合治疗中的作用及其预后因素.方法 回顾分析1990-2006年收治的177例患者,其中单纯化疗37例(中位4周期),化疗(中位3周期)+放疗(中位剂量52 Gy)128例,单纯放疗(中位剂量58 Gy)6例,放疗(中位剂量54 Gy)+化疗(中位5周期)6例.结果 首程化疗后有效(CR+PR)率为65.3%,接受放疗后的为92.8%(x2=28.63,P<0.01).接受放疗的局部控制率(80.9%)优于单纯化疗者(50.0%;x2=14.39,P<0.01);5年总生存率分别为53.4%和18.3%(x2=23.38,P<0.01),无进展生存率分别为45.0%和10.9%(x2=23.46,P<0.01).首程化疗后有效与无效(SD+PD)者接受放疗的局部控制率、5年总生存率均明显优于单纯化疗者[83.5%与76.2%优于50.0%(x2=14.13,P<0.01;x2=5.78,P<0.01)、56.2%与48.6%优于18.3%(x2=28.87,P<0.05;x2=4.80,P<0.05)].结论 放疗比化疗能显著提高早期结外鼻型NK/T细胞淋巴瘤的有效率、局部控制率和生存率,对化疗后局部肿瘤无效者也有显著疗效.根治性放疗应成为早期鼻型NK/T细胞淋巴瘤的首选治疗手段.     

97例ⅠA 期霍奇金淋巴瘤患者的疗效分析

背景与目的:有研究表明霍奇金淋巴瘤(Hodgkin's lymphoma,HL)的治疗应根据临床分期和危险因素不同而采取不同的综合治疗策略,但Ⅰ A期HL的最佳治疗方案尚未明确,本研究对Ⅰ A期HL的治疗和预后情况进行回顾性分析.方法:根据预后因素将97例临床Ⅰ A期HL患者分为预后非常好(very favorable,VF)组、预后好(favorable,F)组和预后不好(unfavorable,UF)组,并分析其总生存(overall survival,OS)率、无病生存(disease-free survival,DFS)率、第二原发肿瘤和死亡原因,多因素分析影响预后的因素.结果:VF组、F组和UF组分别有7例(7.2%)、72例(74.2%)和18例(18.6%).全组患者的中位随访时间为65个月.接受治疗后90例(92.8%)患者达完全缓解(CR),其5年和10年OS率分别为87.7%和76.3%,5年和10年DFS率分别为79.4%和74.5%.VF组、F组、UF组的5年OS率分别为100%、88.9%、78.1%,10年OS率分别为100%、88.4%、39.1%(P=0.292);5年DFS率分别为100%、86.3%、73.6%,10年DFS率分别为87.2%、71.8%、34.5%(P=0.032).多因素分析表明,影响OS的因素包括病理类型(P=0.056)和是否复发(P=0.001),近期疗效是影响DFS的主要因素(P=0.024).全组复发率为18.6%,单纯放疗和联合放化疗者的复发率差异无统计学意义(x2=0.072,P=0.788).第二原发肿瘤的发生率为5.2%,其中2例为非霍奇金淋巴瘤.死亡12例(12.4%),均为单纯放疗患者.结论:临床Ⅰ A期HL患者单纯放疗或联合放化疗90%以上可达CR.联合放化疗的远期疗效均优于单纯放疗.病理类型、首次治疗疗效和是否复发是Ⅰ A期HL患者生存的主要影响因素.     

Long-term clinical outcome of Helicobacter pylori eradication for gastric mucosa-associated lymphoid tissue lymphoma with a reference to second-line treatment

BACKGROUND: The goals of the current study were to elucidate the long-term outcome of Helicobacter pylori eradication therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to clarify the therapeutic efficacy of stomach-conserving treatments for patients not responding to eradication therapy. METHODS: Ninety-six patients with gastric MALT lymphoma, including 17 patients with areas of diffuse large B-cell lymphoma, were treated by H. pylori eradication. Patients not responding to eradication therapy underwent either a gastrectomy, multiagent chemotherapy, oral monochemotherapy (OMC), or radiotherapy (RT). Predictive factors for the response to eradication therapy, overall survival (OS), and event-free survival (EFS) were determined by the Kaplan-Meier analysis with the log-rank test. The efficacy of second-line treatment was compared between OMC and RT. RESULTS: After eradication therapy, 62 (65%) patients achieved complete disease remission (CR). Transient histologic disease recurrence was confirmed in 4 (6.5%) of 62 patients with CR during the follow-up (median, 37.5 months). The OS and EFS probabilities after 5 years were 0.96 and 0.80, respectively. Second-line treatment was performed in 31 patients; gastrectomy in 4 patients, multiagent chemotherapy in 5 patients, OMC in 12 patients, and RT in 10 patients. There were no differences in the CR rate, OS, EFS, or toxicity between the OMC and RT groups. CONCLUSIONS: H. pylori eradication therapy was an effective first-line treatment for patients with gastric MALT lymphoma, which led to a favorable long-term outcome. OMC and RT had an equivalent efficacy as a second-line treatment in nonresponding patients to eradication therapy.     

Localized extranodal lymphoma of the head and neck: retrospective analysis of a series of 107 patients from a single institution

PURPOSE: To retrospectively analyze the outcome and patterns of relapse in localized extranodal non-Hodgkin's lymphoma of the head and neck (HN-NHL) after radiotherapy alone or combined modality treatment. PATIENTS AND METHODS: A retrospective analysis of 107 patients with HN-NHL was performed. Relapse patterns, overall survival (OS) and relapse-free survival (RFS) were analyzed. Only stage I (n=50) and stage II (n=57) patients were included with either low-grade (n=21) or high-grade (n=86) lymphoma. Fifty-nine patients were treated with radiotherapy (RT) alone and 48 patients received combined-modality treatment (CMT) consisting of chemotherapy (CHOP or CHOP-like) followed by radiotherapy. The volumes of irradiation included local field (n=24), involved field (n=13) and extended field (n=70). The median age at diagnosis was 63 years (range, 17-86 years). RESULTS: The overall response rates (CR+PR) in the radiotherapy group and the combined modality group were 100% and 96%, respectively. With a median follow-up of 49.4 months, 29 of 59 patients after RT alone (37%) and 30 of 48 patients after CMT (62%) were disease-free. In the whole series the projected five-year OS and RFS were 58.7% and 61.8%. At univariate analysis of clinical variables with potential impact on survival including age, stage, histology, IPI score, single or combined treatment and volumes of irradiation, only age and, to a limited extent, type of treatment influenced OS (age < or =60 years 79%, >60 years 41%, P < 0.001; RT alone 54.9%, CMT 62.8%, P = 0.0487) and RFS (< or =60 years 75%, >60 years 50%, P < 0.001; RT alone 54%, CMT 71%, P = 0.039). Better OS and RFS rates were obtained in patients with stage II and high-grade disease treated with CMT (five-year OS and RFS 63% and 69%, respectively; the corresponding values for RT alone were 38% and 34%). The final model of the multivariate analysis retained only age (< or =60 years) as a significant prognostic factor for both RFS and OS (P < 0.001). In the whole series, the sites of relapse were mainly systemic (n = 32/40, 80%) and in-field relapses were rare (n = 3/40, 7.5%). CONCLUSION: HN-NHL is characterized by a high risk of relapse, particularly at distant sites. Older patients have a significantly worse prognosis. Radiotherapy offers a very good local control rate although combined modality treatment possibly produces better RFS and OS, especially for stage II and high-grade disease. Better systemic approaches are warranted for a more consistent impact on survival in this particular subset of extranodal lymphoma. However, radiotherapy alone may offer a feasible and effective modality for patients who cannot tolerate more aggressive treatments. Extended-field radiotherapy and the treatment of a larger number of uninvolved lymph nodal regions does not confer a RFS or OS advantage, either after RT alone or after CMT.     

Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy

PURPOSE: To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT). METHODS AND MATERIALS: This was a retrospective analysis of all patients undergoing potentially curative therapy for adenocarcinoma of the duodenum at Duke University Medical Center and affiliated hospitals between 1975 and 2005. Overall survival (OS), disease-free survival (DFS), and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis evaluated the effect of CT-RT on clinical endpoints. RESULTS: Thirty-two patients were identified (23 M, 9 F). Median age was 60 years (range, 32-77 years). Surgery alone was performed in 16 patients. An additional 16 patients received either preoperative (n = 11) or postoperative (n = 5) CT-RT. Median RT dose was 50.4 Gy (range, 12.6-54 Gy). All patients treated with RT also received concurrent 5-fluorouracil-based CT. Two patients treated preoperatively had a pathologic complete response (18%), and none had involved lymph nodes at resection. Five-year OS, DFS, and LC for the entire group were 48%, 47%, and 55%, respectively. Five-year survival did not differ between patients receiving CT-RT vs. surgery alone (57% vs. 44%, p = 0.42). However, in patients undergoing R0 resection, CT-RT appeared to improve OS (5-year 83% vs. 53%, p = 0.07). CONCLUSIONS: Local failure after surgery alone is high. Given the patterns of relapse with surgery alone and favorable outcomes in patients undergoing complete resection with CT-RT, the use of CT-RT in selected patients should be considered.     

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study.

BACKGROUND: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program. PATIENTS AND METHODS: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas). RESULTS: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms. CONCLUSIONS: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL.     

Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma

BackgroundThe purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT).Patients and methodsData on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4–27.3). Demography at ASCT was 61% stage IV, median age 31 years (18–69), median prior treatment (tx) regimens 3 (2–7), median Hasenclever index 3 (0–6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease.ResultsPost-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years.ConclusionThese data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.     

Combination carboplatin and radiotherapy in the management of stage II testicular seminoma: comparison with radiotherapy treatment alone.

PURPOSE: To assess the results of treatment in 33 patients with stage IIA/B seminoma who were treated with carboplatin and radiotherapy (RT) between January 1989 and December 1996. PATIENTS AND METHODS: Thirty patients received single course single agent carboplatin (400 mg/m2 or area under curve (AUC 7), two patients received two courses carboplatin, and one patient received single course carboplatin and etoposide, all 4-6 weeks prior to infra-diaphragmatic RT. Results were retrospectively compared with those obtained for 80 patients treated from 1970 to 1998 with radiotherapy alone. RESULTS: There was minimal toxicity associated with the use of carboplatin prior to RT. With a median follow-up of 4 years (range 2-70 months) 2/33 patients treated with chemotherapy and RT have relapsed, 5-year relapse free survival (RFS) = 96.9% (95% confidence interval (CI) 72.9-99.4%), and one patient has died of progressive disease, 5-year overall survival (OS) = 96.7%. With a median follow-up of 11.2 years (range 6 months to 25.8 years) 15/80 patients treated with RT alone have relapsed, 5-year RFS = 80.7% (95% CI 70.1-87.9%), including 13/61 patients treated with infra-diaphragmatic RT, 5-year RFS = 77.9%, and 2/19 treated with additional supra-diaphragmatic RT, 5-year RFS = 89.5% (P = 0.277). Eleven out of 80 patients have died, 5-year OS = 94.7%. For stage IIA, 1/14 patients treated with chemotherapy and RT have relapsed, 5-year RFS = 92.3%, compared with 5/34 treated with infra-diaphragmatic RT alone 5-year, RFS = 84.9% (P = 0.527). For stage IIB, 1/19 patients relapsed (at 69 months) following chemotherapy and RT (5-year RFS = 100%), whereas 8/27 relapsed following infra-diaphragmatic RT alone, 5-year RFS = 69.4% (P = 0.0595). CONCLUSION: Infradiaphragmatic RT alone cures the majority of patients with stage II seminoma, but the relapse rate remains high particularly for patients with stage IIB disease. As compared with historical controls, carboplatin with RT appears to reduce the relapse rate in stage II seminoma with minimal additional toxicity and the results approach statistical significance for stage IIB patients. Confirmation would require a phase III randomized comparison.     

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.     

Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.

BACKGROUND: The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL. PATIENTS AND METHODS: Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide. RESULTS: No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse. CONCLUSIONS: Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.     

Predictive impact of MGMT promoter methylation in glioblastoma of the elderly

O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation identifies a subpopulation of glioblastoma patients with more favorable prognosis and predicts a benefit from alkylating agent chemotherapy (CT). Little is known about its prevalence and clinical significance in older glioblastoma patients. We studied 233 glioblastoma patients aged 70 years or more (144 males, 89 females, median age: 74 years, range: 70.0-86.6 years), who were prospectively enrolled in the German Glioma Network, for MGMT promoter methylation by methylation-specific PCR (MSP) in all patients and DNA pyrosequencing in 166 patients. MGMT data were correlated with patient outcome. Median progression-free survival (PFS) was 4.8 months (95% CI: 4.3-5.3) and median overall survival (OS) was 7.7 months (95% CI: 6.3-9.0). MGMT promoter methylation was detected by MSP in 134 patients (57.5%). For the whole cohort, PFS was 5.2 versus 4.7 months (p = 0.207) and OS was 8.4 versus 6.4 months (p = 0.031) in patients with versus without MGMT promoter methylation. Patients with MGMT methylated tumors had longer PFS when treated with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT alone. Patients with MGMT unmethylated tumors appeared to derive no survival benefit from CT, regardless of whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated longer OS when pyrosequencing revealed >25% MGMT methylated alleles. Taken together, MGMT promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent CT.     

Role of induction chemotherapy and bone marrow transplantation in adult lymphoblastic lymphoma: A report on 62 patients from a single center

Objective: To describe the outcome of an unselected large series ofpatients with lymphoblastic lymphoma (LBL) treated in a single institution.Patients and methods: Sixty-two patients were treated between 1980 and1992. Induction chemotherapy (CT) to achieve complete response (CR) was:French Multicenter Acute Lymphoblastic Leukemia (ALL) protocols (38),non-Hodgkins Lymphoma (NHL) protocols (20). Thirty patients underwenttransplant after achieving CR (allogeneic 12; autologous 18).Results: Forty-six patients (74%) achieved CR and 16 (26%)failed to respond. The patients who received an ALL induction had an89% CR rate, while the CR rate was 52% in patients whoreceived a NHL-like regimen. With a median follow-up of 93 months (range36–187), the actuarial overall survival (OS) rate for all patients is49% at five years and 41% at 10 years, and the actuarialevent-free survival (EFS) rate is 45% and 37%. OS and EFS inthe grafted population are, respectively, 60% and 56% at fiveyears. Our results also show a trend toward a longer OS in allograftedgroup.Conclusions: ALL induction therapy is more effective than the NHL-likeregimen for augmenting the CR rate. Autologous or allogeneic transplantationshould be considered as consolidation therapy in high-risk group patients.     

Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy

The aim of this study was to determine the outcome for patients with Chang stage M2-3 medulloblastoma (MB) treated with surgery and pre-radiotherapy (RT) chemotherapy (CT). Between 1992 and 2000, 68 patients aged 2.8-16.4 years (median 7.8 years) with M2-3 MB were treated with CT comprising vincristine, etoposide, carboplatin and cyclophosphamide. For 61 patients, CT was followed by craniospinal RT 35 Gy/21 fractions with a posterior fossa (PF) boost, 20 Gy/12 fractions. Twenty-four (35%) irradiated patients received a metastatic boost (mean dose to metastases 47.4 Gy, range 40.0-55.1 Gy). With 7.2-years of median follow-up, overall survival (OS) rates at 3 and 5 years were 50.0% (95% Confidence Interval (CI): 38.1-61.9%) and 43.9% (95% CI: 32.0-55.7%), respectively, event-free survival (EFS) rates at 3 and 5 years were 39.7% (95% CI: 28.1-51.3%) and 34.7% (95% CI: 23.2-46.2%), respectively. Univariate analysis did not demonstrate an impact of age, gender, M stage, extent of resection, RT duration or metastatic boost. For patients commencing RT within 110 days of surgery, EFS was significantly (P=0.04) worse than for those who commenced RT later than this. Response to pre-RT CT was assessable from institutional reports for 44 (65%) patients, and 17 (39%) had a complete response (CR), 15 (34%) a partial response (PR), 4 (9%) stable disease (SD) and 8 (18%) progression. Although CT improved outcome for M0-1 patients in the primitive neuroectodermal tumour (PNET-3) randomised study, and resulted in a high response rate in this study, there has been no apparent improvement in outcome for M2-3 patients when compared with earlier multi-institutional series. Newer approaches such as more intensive CT and RT need to be explored.     

Long-term clinical and functional outcomes after treatment for localized Ewing's tumor of the lower extremity

PURPOSE: Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity. PATIENTS AND METHODS: Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery +/- RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS). RESULTS: Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% (p = 0.21), 73% vs. 47% (p = 0.13), 73% vs. 40% (p = 0.03), and 43% vs. 40% (p = 0.52), respectively, for patients treated with surgery +/- RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery +/- RT group and 68% for the definitive RT group (p = 0.03). The ranges of the TESS for surgery +/- RT vs. RT alone were 70-100 (mean, 94) and 97-100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation. CONCLUSIONS: Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies.