IMRT早期韦氏环DLBCL的长期观察

目的 研究IMRT对原发于韦氏环早期DLBCL的疗效、预后、放射剂量及不良反应。 方法 收集2008—2015年Ⅰ、Ⅱ期韦氏环DLBCL病例 80例,放化疗为主,3例单纯放疗。化疗后CR 24例,PR 53例。原发灶及颈部淋巴结引流区IMRT。采用Kaplan-Meier法计算生存率,Cox模型预后因素分析,不良反应分级使用RTOG标准。 结果 中位随访时间为64个月,5年LRC、OS、PFS率分别为94%、88%、84%。DVH显示PGTV最高、平均和最低剂量分别为54.47、52.27、38.83 Gy。因素分析显示年龄>60岁、LDH升高为OS影响因素(P=0.009、0.002),年龄>60岁、IPI≥2分及LDH升高为PFS影响因素(P=0.001、0.035、0.007)。全组急性口腔黏膜反应1级 12例、2级 53例、3级 8例,晚期不良反应口干1级 16例、2级 13例。 结论 应用IMRT技术治疗原发韦氏环的早期DLBCL,获得了较理想的LRC、PFS、OS率,同时不良反应可耐受。     

Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy

Background  

We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas.     

Long-term follow-up for patients with Ewing's sarcoma of bone treated with adjuvant and neoadjuvant chemotherapy

The long-term results obtained in 252 patients with non-metastatic Ewing's sarcoma of bone treated between March 1972 and June 1988 according to three sequential protocols of treatment were evaluated. Primary tumor was treated with radiotherapy in 125 cases, with surgery in 52 and with surgical resection followed by radiotherapy in 75. In the first protocol (REA 1; 1972-78) chemotherapy was performed with a 3-drug regimen (VCR, CPM, ADM), whereas in the REA 2 protocol (1979-82) and in the REN 1 protocol (1983-88) a 4-drug regimen was used (VCR, CPM, ADM, ACTD). Chemotherapy was delivered as adjuvant treatment in REA 1 and 2, and as neoadjuvant in the last study. At a mean follow-up of 14.8 years, with the 95% of patients with a minimum FU of 10 years, 101 pts (40%) remained continuously free of disease, 144 patients relapsed, two patients died of adriamycin cardiotoxicity and 5 patients developed a second neoplasm. 6% of the patients relapsed 5 or more years after the diagnosis with the latest recurrence registered at the tenth year. Type of local treatment, LDH serum level, chemotherapy protocol and sex were predictive factors of DFS after a multivariate analysis. The possibility of late relapse in Ewing's sarcoma has been confirmed by our retrospective study and for patients with Ewing's sarcoma, a 10-year follow up should be recommended.     

Long-term follow-up of patients treated with radiotherapy alone for early-stage histologically aggressive non-Hodgkin's lymphoma

Historically localised aggressive non-Hodgkin's lymphoma (NHL) has been treated with involved field radiotherapy (RT), chemotherapy, or a combination of both modalities. The current weight of evidence supports a preference for combined modality treatment (CMT). Increased patient age at diagnosis is well recognised as a poor prognostic indicator in NHL, but despite this some perceive CMT as too toxic for use in the elderly. As a result, some older patients continue to be offered RT alone. Here, we present long-term follow-up of 377 adults of all ages treated with RT alone for early-stage diffuse large-cell lymphoma on British National Lymphoma Investigation trials between 1974 and 1997. 10-year cause-specific survival in patients older than 60 years was poor and significantly inferior to that in younger patients (47 and 75% respectively; P<0.001). There is growing evidence that short-course chemotherapy, with or without RT, is superior to RT alone in early-stage aggressive NHL, in elderly as well as in younger patients. Increased age alone should not exclude patients from systemic treatment for early-stage aggressive NHL.     

Prognostic variables in patients with diffuse large-cell lymphoma treated with MACOP-B.

One hundred twenty-six patients with diffuse large-cell lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between April 1981 and June 1986. Univariate and multivariate analyses were performed using overall survival as of September 1989 as the end point. Four independent negative predictors of survival were identified: presence of B symptoms; more than two involved lymph node sites; more than one extranodal site (variables related to tumor burden), and age older than 60, a variable related to the patient's ability to tolerate treatment. Each variable contributed the same relative risk of dying and, accordingly, this simple predictive formula was developed empirically: (4-N) x 30 = the approximate percentage of chance of survival at 5 years. "N" is the number of predictive variables present. The same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed.     

青少年或儿童原发系统性间变大细胞淋巴瘤CHOP为主化疗±放疗的远期疗效

目的 分析青少年儿童原发系统性间变大细胞淋巴瘤(ALCL)患者接受CHOP方案化疗 ±受累野放疗的疗效。方法 回顾分析本院1998—2010年收治的 28例青少年、儿童ALCL患者资料。Ⅰ、Ⅱ期 12例中单纯化疗 2例、综合治疗 10例,Ⅲ、Ⅳ期 16例中单纯化疗 14例、综合治疗 2例。CHOP方案 15例、CHOP联合其他高强度化疗 13例。化疗周期数 3~17个(中位数6个)。放疗多为受累野照射,剂量 39.6~50.0 Gy (中位数45 Gy)。结果 全组患者首程疗后达CR者 25例(89%),3例病变进展。中位随访时间45.3个月。全组 5年无事件生存率为80%,5年OS为93%。疗终达CR者 5年OS为100%,而未达CR者无 5年OS (P=0.000)。≥2个结外器官受侵者 5年无事件生存率为38%,而<2个结外器官受侵者的为85%(P=0.010)。结论 青少年、儿童原发系统性ALCL按成人方案治疗效果满意,但还需要长期随访。     

Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484.

PURPOSE: To compare low-dose (30 Gy) radiotherapy (RT) with observation (OBS) in limited-stage aggressive lymphoma patients achieving complete remission (CR) after chemotherapy, and to measure conversion from partial response (PR) to CR with high-dose (40 Gy) RT. PATIENTS AND METHODS: From 1984 to 1992, stage I (with risk factors) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomly assigned to 30 Gy involved-field RT or OBS. PR patients received 40 Gy RT. RESULTS: Among 172 CR patients, the 6-year disease-free survival (DFS) was 73% for low-dose RT versus 56% for OBS (two-sided P = .05). Failure-free survival (two-sided P = .06), and time to progression (two-sided P = .06) also favored RT. Intent-to-treat analyses yielded similar results. No survival differences were observed. Three RT versus 15 OBS patients relapsed in initial disease sites. At 6 years, failure-free survival was 63% in PR patients; conversion to CR did not significantly influence clinical outcome. CONCLUSION: For patients in CR after CHOP, low-dose RT prolonged DFS and provided local control, but no survival benefit was observed. The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities. Future efforts should be directed toward improved imaging and more effective systemic therapies.     

Advanced diffuse large-cell lymphoma treated with 12-week combination chemotherapy: Natural history of relapse after initial complete response and prognostic variables defining outcome after relapse

Purpose: To define both the natural history of and prognostic factors affecting outcome post relapse from a complete response in advanced stage diffuse large-cell lymphoma.Patients and methods: A total of 468 patients aged 17–74 years received the 12-week duration chemotherapy regimens MACOP-B, VACOP-B and ACOP-12 between 1 April 1981 and 31 December 1995 for advanced stage diffuse large, mixed or immunoblastic lymphoma. Of these 402 entered a complete remission, 97 (24%) of whom subsequently relapsed. Initial staging data, follow-up, and relapse information were analyzed to define the natural history of relapse and also subjected to univariate and multivariate correlation with overall (OS) and failure free survival (FFS).Results: Eleven percent of the relapses were low grade. All other relapses were of intermediate grade with 75% occurring within the first two years, the remainder up until the eleventh year. Median and five-year OS from the time of relapse for intermediate grade relapse were 12 months and 20%; for FFS they were eight months and 18% respectively. Adverse independent factors, for both OS and FFS were: less than one year to relapse, decreasing performance status at relapse, and more than three nodal sites at relapse.Conclusions: Low-grade relapse is not uncommon in patients who initially presented with diffuse large cell lymphoma. As the management of low- and intermediate grade disease is so different biopsy proof of the nature of the relapse is of value. The prognostic factors identified need to be taken into consideration when analyzing results from trials of secondary treatment so as to avoid erroneous conclusions about comparative treatment efficacy.     

Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy

High-dose chemotherapy and whole brain radiotherapy (WBRT) can prolong survival in primary CNS lymphoma (PCNSL) patients, but is often associated with clinically significant cognitive decline. In this study we assessed neuropsychological functioning prospectively in newly diagnosed PCNSL patients treated with induction chemotherapy followed by reduced-dose WBRT. Twelve patients underwent neuropsychological evaluations at diagnosis, after induction chemotherapy, and 6 and 12 months after WBRT. Nine patients completed additional cognitive evaluations 18 and 24 months post-treatment. At diagnosis, patients had impairments in Executive Functions, Verbal Memory, and Motor Speed. There was a significant improvement in Executive Functions (P < 0.01) and Verbal Memory (P < 0.05) following induction chemotherapy, and scores remained relatively stable up to 12 months post-treatment. Among the nine patients who completed a 2-year follow-up, there was a significant improvement in the Executive domain (P < 0.05) and a trend toward a decline in the Verbal Memory domain. Executive and Verbal Memory functions improved following induction chemotherapy, likely due to decreased tumor burden and discontinuation of corticosteroid and anticonvulsant medications. There was no significant cognitive decline up to 24 months post-chemotherapy and reduced-dose WBRT in this group of PCNSL patients, however, difficulties in Verbal Memory and Motor speed persisted over the follow-up period. Preliminary results of this study were presented at: (1) International Primary CNS Lymphoma Collaborative Group (IPCG) Meeting in Orlando, Florida—December, 2006. (2) International Neuropsychological Society (INS) 36th Annual Meeting in Waikoloa, Hawaii—February, 2008.     

IMRT下局限期SCLC放化疗疗效及预后分析

目的 探讨IMRT技术下局限期SCLC放化疗疗效及预后分析。方法 回顾分析2006—2014年于本中心行放化疗的 484例局限期SCLC患者临床资料。IMRT有效者行PCI。采用Kaplan-Meier法计算生存率,Logrank检验进行单因素分析,Cox模型进行多因素分析。结果 全组随访率为93%,中位OS期23.8个月,2、3、5年OS率分别为48.7%、39.8%、28.6%,中位PFS期14.1个月,2、3、5年PFS率分别为34.4%、30.5%、28.3%。SCLC患者IMRT后≥3级骨髓抑制发生率26.9%,≥2级放射性食管炎发生率24.8%,≥2级放射性肺炎发生率18.4%。治疗客观有效率84.5%。单因素分析显示年龄、吸烟史、TNM分期、PCI、放疗前化疗周期数是预后影响因素(P=0.006、0.001、0.047、0.000、0.046),多因素分析显示吸烟史、PCI是影响预后的因素(P=0.001、0.000)。结论 IMRT技术下局限期SCLC放化疗取得了较好疗效,吸烟史、PCI是局限期SCLC的预后影响因素。     

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma.

Elderly patients with advanced-stage diffuse large-cell lymphomas (DLCLs) are either excluded from or under-represented in most clinical trials of combination chemotherapy regimens because they tolerate treatment poorly and usually have a worse outcome. We report two brief weekly chemotherapy regimens designed specifically for elderly patients. Eligible patients were aged 65 to 85 years, had advanced-stage DLCL (diffuse mixed, diffuse large-cleaved or noncleaved, immunoblastic, or diffuse large-cell not otherwise specified). Advanced stage was defined as Ann Arbor stage III or IV or stage I or II with a mass greater than 10 cm or B symptoms. Low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOP-B) accrued 40 patients between March 1983 and September 1985; 65% achieved a complete response (CR), there were two toxic deaths, the actuarial failure-free survival (FFS) is 19%, disease-specific survival (DSS) 30%, and overall survival (OS) 28%, with a maximum follow-up of 6 years. The regimen of etoposide, doxorubicin, vincristine, bleomycin, and prednisone (VABE) accrued 32 patients between July 1985 and June 1987; 63% achieved a CR, there were two toxic deaths, and the actuarial FFS is 34%, DSS 45%, and OS 36%, with a maximum follow-up of 4 years. There is no difference in FFS, DSS, or OS between these two regimens. VABE caused more myelosuppression and infectious complications, although the toxic death rates were similar. We prefer LD-ACOP-B because follow-up is longer and toxicity is less.     

Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas

BACKGROUND:

Patients with large, high‐grade, extremity soft tissue sarcomas (STS) are at significant risk for distant recurrence and death. A regimen of preoperative chemotherapy consisting of mesna, Adriamycin (doxorubicin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT) and followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. We report the long‐term follow‐up data on 48 patients treated with this regimen compared to an historical matched‐control patient population.

METHODS:

Adult patients with high‐grade extremity STS ≥ 8 cm were treated with 3 cycles of preoperative chemotherapy combined with 44 Gy of RT followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy of RT was delivered postoperatively.

RESULTS:

Patients received the MAID/RT regimen from 1989 through 1999. After a median follow‐up of 9.3 years in surviving patients in the MAID group and 13.2 years in surviving patients in the control group, the 7‐year disease‐specific and overall survival rates were 81% and 50% (P = .004) and 79% and 45% (P = .003) for the MAID and control patients, respectively. Five of 11 patients in the MAID group and 7 of 25 control patients died of sarcoma ≥5 years after treatment. One patient in the MAID group developed a fatal myelodysplasia at 53 months.

CONCLUSIONS:

For patients with high‐risk, extremity STS, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery are sustained even with long‐term follow‐up. Cancer 2012. © 2011 American Cancer Society.     

Outcomes in patients with splenic marginal zone lymphoma and marginal zone lymphoma treated with rituximab with or without chemotherapy or chemotherapy alone

BACKGROUND: The optimal management of patients with splenic marginal zone lymphoma/marginal zone lymphoma (SMZL) is controversial. The objective of this retrospective study was to compare the outcomes of patients with SMZL who received treatment with rituximab, rituximab plus chemotherapy, or chemotherapy alone. METHODS: The Leukemia Service database was searched for patients with splenic lymphoma who were registered between May 1995 and October 2004. The indications for treatment were the same as those used for patients with chronic lymphocytic leukemia. RESULTS: SMZL was confirmed in 70 patients. The median age was 64 years. The median number of CD20 molecules per cell was 69 x 10(3). Forty-three patients required systemic therapy; rituximab in 26 patients, chemotherapy plus rituximab in 6 patients, and chemotherapy alone in 11 patients. Ten additional patients underwent splenectomy, and 17 patients were in the observation group. The overall response rates were 88% with rituximab, 83% with rituximab plus chemotherapy, and 55% with chemotherapy alone; the 3-year survival rates were 95%, 100%, and 55%, respectively. The 3-year failure-free survival (FFS) rates were 86%, 100%, and 45% in the rituximab, rituximab plus chemotherapy, and chemotherapy alone groups, respectively. Rituximab treatments resulted in longer survival and FFS compared with chemotherapy. Rituximab alone resulted in disappearance of splenomegaly in 92% of patients and normalization of absolute lymphocyte counts. In univariate analysis, younger age and rituximab-based therapy were predictive of longer FFS. CONCLUSIONS: Rituximab with or without chemotherapy was found to have major activity in patients with SMZL. These results may be associated with high levels of cellular CD20 antigen sites. Rituximab should be the treatment of choice, at least in older patients with SMZL who have comorbid diseases.     

Brief chemotherapy and involved-region irradiation for limited-stage diffuse large-cell lymphoma: an 18-year experience from the British Columbia Cancer Agency.

PURPOSE: To evaluate clinical outcome of patients with limited-stage diffuse large-cell lymphoma (DLCL) treated with three cycles of chemotherapy followed by involved-region irradiation (IRRT). PATIENTS AND METHODS: Adults with limited-stage DLCL were treated with brief doxorubicin-containing chemotherapy regimens between 1980 and 1998. IRRT was administered 3 to 4 weeks after the third chemotherapy treatment in a dose equivalent to 30 Gy in 10 fractions. RESULTS: Three hundred and eight patients (median age, 64 years) were included, and 299 experienced complete remission. After a median follow-up of 86 months, 64 patients developed progressive disease, and 104 patients died (43 from lymphoma, three from toxicity, and 58 from other causes). Actuarial overall and progression-free survival (PFS) rates were, respectively, 80% and 81% at 5 years and 63% and 74% at 10 years. For subgroups identified using the Miller modification of the International Prognostic Index (IPI), the overall survival rates at 5 and 10 years were, respectively, 97% and 89% (no factors), 77% and 56% (one or two factors), and 58% and 48% (three or four factors), and the 5-year and 10-year PFS rates were, respectively, 94% and 89% (no factors), 79% and 73% (one or two factors), and 60% and 50% (three or four factors). Men with testicular presentation, had a definitely inferior outcome. CONCLUSION: Long-term outcome with three cycles of doxorubicin-based chemotherapy and IRRT confirms that this is a successful approach for the majority of patients with limited-stage DLCL. Subgroups with worse prognoses can be identified, and these patients should be offered alternative treatment approaches.     

Long-term follow-up of patients with Stage III follicular lymphoma treated with primary radiotherapy at Stanford University

PURPOSE: To report the long-term survival and late toxicity data of Stage III follicular lymphoma patients treated with primary radiotherapy.METHODS AND MATERIALS: Sixty-six patients with Stage III follicular small cleaved (FSC) or follicular mixed (FM) non-Hodgkin's lymphoma were treated with total lymphoid irradiation (61 patients) or whole body irradiation (5 patients) as their primary treatment modality from 1963 to 1982 at Stanford University. Adjuvant chemotherapy was given to 13 patients. RESULTS: Median follow-up was 9.5 years with a range of 0.5-24.3 years. Median overall survival, cause-specific survival, freedom from relapse, and event-free survival were 9.5, 18.9, 7.1, and 5.1 years, respectively. Few initial relapses or lymphoma-related deaths were seen beyond the first decade of follow-up. Patient age and number of disease sites were the two strongest predictors of overall survival. The cohort of patients with limited Stage III disease demonstrated an 88% freedom from relapse and a 100% cause-specific survival with up to 23.5 years follow-up. CONCLUSION: The long-term survival data for Stage III FSC or FM non-Hodgkin's lymphoma treated with primary radiotherapy are at least comparable and possibly better than results achieved with other therapeutic approaches. Patients with limited Stage III disease do particularly well. Whether these results are superior to an initial approach of deferred therapy until clinically indicated is currently unknown.