FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma

Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET-positive patients progressed and 2 died. Three of 61 FDG-PET-negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P < .001) and OS (P < .01). For prediction of PFS, interim FDG-PET was as accurate after two cycles as later during treatment and superior to computerized tomography (CT) at all times. In regression analyses, early interim FDG-PET was stronger than established prognostic factors. Other significant prognostic factors were stage and extranodal disease. Early interim FDG-PET is a strong and independent predictor of PFS in HL. A positive early interim FDG-PET is highly predictive of progression in patients with advanced-stage or extranodal disease.     

Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer

AimA systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer.MethodsBy searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots.ResultsTwenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti-EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797–0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900–1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817–1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990–1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias.ConclusionThe use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials.     

The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma

The prognostic value of interim positron emission tomography (PET) was evaluated after 2 cycles of doxorubicin, bleomycin, vinblastin and dacarbazine in classical Hodgkin lymphoma patients (n = 229), based on Deauville criteria. In early stage non‐bulky disease, bulky stage II disease, advanced stage low International Prognostic Score (IPS ≤2) and advanced stage (IPS ≥3), 3‐year progression‐free survival rates in PET2‐negative vs. PET2‐positive groups were 95·9% vs. 76·9% (P < 0·0018), 83·3% vs. 20·0% (P = 0·017), 77·0% vs. 30·0% (P < 0·001) and 71·0% vs. 44·4%(P = 0·155), respectively. The outcome after positive PET2 was better than previously reported. The results from non‐randomized studies of PET2‐guided therapy would be valuable with careful interpretation.     

Lymphopenia following the completion of first-line therapy predicts early relapse in patients with diffuse large B cell lymphoma

Early relapse is a parameter that affects clinical outcomes in relapsed diffuse large B cell lymphoma (DLBCL). The prognostic value of lymphopenia following the completion of first-line therapy and the relationship between lymphopenia and early relapse are unknown. Therefore, we studied the role of absolute lymphocyte count (ALC) on early relapse. We retrospectively analyzed de novo DLBCL patients who were treated with rituximab-containing treatment between 2003 and 2010. The median age at the time of diagnosis of 59 DLBCL patients was 71 years. We identified no association between ALC at diagnosis and ALC following the completion of first-line therapy. Among all patients analyzed, 13 (22%) patients were confirmed to exhibit early relapse. Low ALC following the completion of first-line therapy was significantly associated with early relapse by univariate analysis [hazard ratio (HR) = 4.05; 95% confidence interval (CI), 1.11–14.73; P = 0.02] and multivariate analysis (HR = 4.66; 95% CI, 1.24–17.48; P = 0.023). The low ALC group tended to have worse outcomes than the high ALC group with lower rates of progression-free survival (66% and 74%, respectively; P = 0.13) and overall survival (74% and 86%, respectively; P = 0.09), but these differences did not reach statistically. Lymphopenia following the completion of first-line therapy can be used as a marker to predict early relapse.     

Small bowel non-Hodgkin's lymphoma remaining in complete remission by surgical resection and adjuvant rituximab therapy

A 44-year-old man was referred to our hospital with intermittent abdominal pain. Because distention of fluid- and gas-filled loops of small intestine was proved by X-ray, the patient was diagnosed as having small bowel obstruction. A laparotomy revealed a segmental stenosis in the jejunum, which showed diffuse thickening of the intestinal wall. Some mesenteric lymph nodes were swollen. Pathological examination was defined. We diagnosed diffuse large B-cell lymphoma based on the pathological findings of diffuse transmural infiltration of large lymphoid cells and flow-cytometric analyses. Rituximab was administered as adjuvant therapy at weekly doses of 375 mg/m2. Four cycles were performed every 6 mo and he remained CR. Rituximab may be effective as adjuvant therapy.     

中医药治疗胆囊切除术后综合征的Meta分析

目的:以系统评价的方式分析中医药治疗胆囊切除术后综合征(PCS)的临床疗效。方法:系统地回顾了28篇符合纳入标准的随机对照试验文献并进行Meta分析,时间跨度为2004至2018年。OR值以及95%置信区间(CI)由每篇纳入的文献的原始数据中获得,经过计算发现各研究之间存在低异质性。结果:采用中医药的治疗组临床症状缓解率明显高于对照组(OR=5.47,95%CI 4.37~6.85,P<0.01)。结论:中药能有效改善PCS相关症状,相比于单纯西药对症治疗具有一定的优势。     

Clinical impact of FDG-PET/CT in the planning of radiotherapy for early-stage Hodgkin lymphoma

BACKGROUND: Early-stage Hodgkin lymphoma (HL) has excellent survival rates but carries a high risk of late treatment-related adverse effects. Modern, individualised therapeutic strategies require an accurate determination of the extent of the disease. This study investigated the potential impact of 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomogrpahy (FDG-PET/CT) in the planning of involved field radiotherapy (IFRT). PATIENTS AND METHODS: Thirty patients received staging FDG-PET/CT before therapy, and IFRT after a short course of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. IFRT planning was performed using only the CT data from the FDG-PET/CT scan. Later, the IFRT planning was performed anew using the FDG-PET/CT data as basis for contouring. RESULTS: In 20 out of 30 patients, the radiotherapy (RT) course was unaffected by the addition of FDG-PET/CT. FDG-PET/CT would have increased the irradiated volume in seven patients where the volume receiving a minimum of 90% of the target dose was increased by 8-87%. FDG-PET/CT decreased the volume in two patients where the volume was reduced by 18% and 30%. CONCLUSIONS: When used for RT planning, FDG-PET/CT results in larger IFRT treatment volumes. If FDG-PET/CT is introduced to RT planning, the method should be accompanied by a change in RT treatment strategy, aiming at more targeted therapy in order to best avoid radiation to normal tissues.     

Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP-BLEO regimens

OBJECTIVES: We conducted a randomized clinical trial to evaluate the role of interferon alfa 2b (IFN) as maintenance therapy in patients with diffuse large B-cell lymphoma with high or high-intermediate clinical risk on complete remission (CR) after CHOP-BLEO regimens. METHODS: Patients were initially treated with CHOP-BLEO regimens (which include increased doses of cyclophosphamide and epirubicine, instead of doxorubicin). If the patients achieved CR they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU, three times at week by 1 yr, or no treatment (control group). RESULTS: Two hundred and twenty-three patients were considered as candidates for the study. They were of high (80%) or high-intermediate (20%) clinical risk; additionaly most patients had poor prognostic factors such as high levels of beta 2 microglobulin, lactic dehydrogenase levels, bulky disease (defined as a tumor mass >10 cm) or multiple extranodal involvement. In an intent-to-treat analysis all patients were evaluable to efficacy and toxicity. Median follow-up was 45 months, the estimated 5-yr overall survival and event-free survival (EFS) for patients who received IFN were 71% (95% confidence interval (CI): 61-83%) and 57% (95% CI: 39-69%), respectively, values which were not statistically different from the control group: 69% (95% CI: 63-79%) and 54% (95% CI: 37-63%), respectively (p=0.2). Toxicity was mild. CONCLUSIONS: These results suggest that IFN used as maintenance therapy at these doses and schedules is not useful in aggressive malignant lymphoma when more intensive chemotherapy has been employed during induction treatment. Nevertheless, follow-up is too short, and long-term follow-up would be necessary in order to draw definitive conclusions. Probably, an multicenter study is necessary to define the role of IFN as maintenance therapy in this patient setting.     

2-year complete remission after withdrawal of methotrexate in a rectal methotrexate-associated diffuse large B-cell lymphoma

A 71-year-old man, who had been receiving methotrexate (MTX) and prednisolone for the treatment of rheumatoid arthritis, was admitted to our hospital in August of 2004 with rectal hemorrhage. Histological examination of an ulcerative lesion of the rectum revealed diffuse large B-cell lymphoma (DLBCL). Chemotherapy with the CHOP regimen with dose reduction following cessation of MTX was initiated. However, the patient experienced septic shock secondary to febrile neutropenia and was then followed up without chemotherapy. The DLBCL rectal lesion regressed spontaneously thereafter and had resolved completely without treatment 2 years after the initial presentation, suggesting that the withdrawal of MTX led to regression of the DLBCL. The DLBCL in our patient is compatible with MTX-associated lymphoproliferative disorders. Immunoglobulin gene rearrangement and Epstein-Barr virus (EBV) infection found in tumor cells indicated that the EBV was involved in the monoclonal proliferation of B-cells in this patient whose immune function was suppressed by MTX therapy.     

Biomodulatory metronomic therapy induces PET‐negative remission in chemo‐ and brentuximab‐refractory Hodgkin lymphoma

There are limited reports that baseline peripheral absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute lymphocyte count (ALC) and serum β2‐microglobulin level independently predict survival in patients with diffuse large B‐cell lymphoma (DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index (IPI) in patients with newly‐diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC (P = 0·036), AMC (P = 0·028) and serum β2‐microglobulin level (P < 0·001), poor performance status (P < 0·001) and high number of extranodal disease sites (P = 0·0497) as independent unfavourable predictors of OS; serum β2‐microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum β2‐microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL.     

Safety of fast-track rehabilitation after gastrointestinal surgery: Systematic review and meta-analysis

AIM: To compare the safety of fast-track rehabilitation protocols (FT) and conventional care strategies (CC), or FT and laparoscopic surgery (LFT) and FT and open surgery (OFT) after gastrointestinal surgery.METHODS: We searched MEDLINE, WHO International Trial Register, Embase and The Cochrane Central Register of Controlled Trials up to 2014 for randomized controlled trials (RCTs) comparing FT and CC or comparing LFT and OFT, with 10 or more randomized participants and about 30 d follow-up. Two reviewers independently extracted data on complications, anastomotic leak, obstruction, wound infection, re-admission between FT and CC or LFT and OFT after gastrointestinal surgery.RESULTS: Twenty-four RCTs of FT vs CC or LFT vs OFT were included. Compared with CC, FT reduced overall complications and wound infection. However, anastomotic leak, obstruction and re-admission were not significantly reduced. The pooled risk ratio (RR) of 0.69 (95%CI: 0.60-0.78; P < 0.001), pooled RR of 0.71 (95%CI: 0.57-0.88; P < 0.001), pooled RR of 0.93 (95%CI: 0.68-1.25; P > 0.05), a pooled RR of 0.87 (95%CI: 0.67-1.15; P > 0.05) and pooled RR of 0.94 (95%CI: 0.73-1.22; P > 0.05) respectively. Compared with OFT, LFT reduced complications, with a pooled RR of 0.66 (95%CI: 0.54-0.81; P < 0.001).CONCLUSION: FTs are safe after gastrointestinal surgery. Additional large, prospective RCTs should be conducted to establish further the safety of this approach.