Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma

Purpose

The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study.

Methods

From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease.

Results

Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p?=?0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p?=?0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n?=?37, 63 %), ΔSUVmaxPET0-2?=?<71 % or TMTV0 >225 ml (n?=?17, 29 %), and ΔSUVmaxPET0-2?=?<71 % and TMTV0 >225 ml (n?=?5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively.

Conclusion

TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.     

Defining the optimal method for measuring baseline metabolic tumour volume in diffuse large B cell lymphoma

Purpose

Metabolic tumour volume (MTV) is a promising prognostic indicator in diffuse large B cell lymphoma (DLBCL). Optimal thresholds to divide patients into ‘low’ versus ‘high’ MTV groups depend on clinical characteristics and the measurement method. The aim of this study was to compare in consecutive unselected patients with DLBCL, different software algorithms and published methods of MTV measurement using FDG PET.

Method

Pretreatment MTV was measured on 147 patients treated at Guy's and St Thomas’ Hospital. We compared 3 methods: SUV ≥2.5, SUV ≥41% of maximum SUV and SUV?≥?mean liver uptake (PERCIST) and compared 2 software programs for measuring SUV ≥2.5; in-house ‘PETTRA’ software and Hermes commercial software.

Results

There was strong correlation between MTV using the 4 methods, although derived thresholds were very different for the 41% method. Optimal cut-offs for predicting PFS ranged from 166–400cm³. All methods predicted survival with similar accuracy. 5y-PFS was 83–87% vs. 42–44% and 5y-OS was 85–89% vs. 55–58% for the low- and high-MTV groups, respectively. Interobserver variation in 50 patients showed excellent agreement, though variation was lowest using the SUV?≥?2.5 method. The 41% method was the most complex and took the longest time.

Conclusion

All methods predicted PFS and OS with similar accuracy, but the derived cut-off separating good from poor prognosis varied markedly depending on the method. The choice of the optimal method should rely primarily on prognostic value, but for clinical use needs to take account of ease of use and reproducibility. In this study, all methods predicted prognosis, but SUV?≥?2.5 had the best inter-observer agreement and was easiest to apply.

     

Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma

Introduction

Our aim was to study the prognostic value of two new ¹⁸F-FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). We examined the total tumor surface (TTS), describing the tumor–host interface, and the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation.

Methods

We retrospectively included 215 patients with DLBCL. Patients underwent initial ¹⁸F-FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimens (27%). The TMTV was measured using a fixed threshold value of 41% of SUVmax. To calculate TTS and TVSR, the surface was measured using an in-house software based on the marching cube algorithm. Spearman’s rank correlation coefficient (ρ) was computed between TMTV, TTS, and TVSR, and ROC analysis was performed. Survival functions at 5 years were studied using a Kaplan-Meier method and uni/multivariate Cox analysis.

Results

TVSR was poorly correlated with TMTV (ρ?=?0.5) and TTS (ρ?=?0.26), while TTS was highly correlated with TMTV (ρ?=?0.94) and was, therefore, excluded from the analysis. TMTV had the highest area under the ROC curve (0.711) and the best sensitivity (0.797), while TVSR had the best specificity (0.745). The optimal cut-off values to predict 5-year OS were 222 cm³ for TMTV and 6.0 cm for TVSR. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining the International Prognostic Index (IPI), the type of chemotherapy, TMTV, and TVSR, all parameters were independent and significant prognostic factors (HR [95%CI]: IPI 1.4 [1.1-1.8], type of chemotherapy 4.5 [2.0-10.5], TMTV 2.8 [1.4-5.5], TVSR 2.1 [1.3-3.4]). A synergistic effect between TMTV and TVSR was observed in a Kaplan-Meier analysis combining the two parameters.

Conclusions

TVSR measured on the initial ¹⁸F-FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy.

     

Radiation therapy of localized diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is most frequently encountered non-Hodgkin's lymphoma in Japan, and about half of the cases present as Ann-Arbor stage I or II localized disease. Randomized clinical trials have revealed that chemotherapy combined with radiation therapy of the involved field yields superior outcome compared with chemotherapy alone. However, optimal chemotherapy cycles remain to be studied. Short-course chemotherapy, such as 3 cycles of CHOP, seems to be adequate for low bulk tumors, and full-course chemotherapy, such as 6-8 cycles of CHOP, seems to be required for larger tumors. Involved field radiation is a regional radiation that includes involved lymph nodes or extranodal sites, although the details vary between institutes. The precise definition of involved field radiation must be examined and clarified. The dose of involved field radiation after chemotherapy is also controversial. Most researchers apply at least 30 Gy to sites in complete remission, whereas a larger dose seems to be necessary for sites in partial remission. Stratification according to various prognostic factors is mandatory to tailor the management of localized diffuse large B-cell lymphoma.     

Tumor volume: an independent predictor of outcome for laryngeal cancer

PURPOSE: Other studies have shown a relationship between the volume of laryngeal tumors and local control when treated with radiation therapy. Our purpose was to determine the relationship between tumor volume, clinical staging, and several histologic abnormalities to local control in patients treated with initial surgery. METHOD: Tumor volume was calculated from pretreatment CT scans in 52 patients with squamous cell carcinoma treated surgically. The presence of perineural and lymphatic spread as well as cartilage and vessel invasion were obtained from histology. All cases had at least a 2 year clinical follow-up after initial surgery. Statistical analysis consisted of Mantel-Haneszel chi2-tests and Fisher exact test. RESULTS: Local control rate was 92%. Tumor volume and cartilage invasion were associated with local control (p < 0.05). Local control rate for tumors with volumes of < 16 cm3 was 98% compared with 40% for tumors with volumes of > 16 cm3 (p < 0.05). Evidence of cartilage invasion was associated with increased likelihood of local recurrence. There was no significant association between local control and perineural, vascular, or lymphatic tumor spread. We found a marginally significant association between clinical T-stage and local control (p = 0.05). CONCLUSION: Pretreatment CT volumes are useful in predicting local control in laryngeal carcinoma treated with surgery. Of the histologic features studied, only cartilage invasion was significant in predicting tumor control.     

Acute tumor lysis syndrome caused by palliative radiotherapy in patients with diffuse large B-cell lymphoma

Acute tumor lysis syndrome (TLS) is a condition that results from the rapid destruction of tumor cells accompanied with a massive release of cellular breakdown products. Acute renal failure resulting from TLS has been reported in cases of hematologic malignancies, spontaneous or treatment induced, the latter especially by chemotherapy. We present the case of a patient with diffuse large B-cell lymphoma who developed radiotherapy-induced TLS and subsequently acute renal failure. He presented with a large mediastinal tumor compressing the airway, thus causing dyspnea. After 6 Gy/3 fractions/3 days of palliative radiotherapy for the tumor, a decrease in urine volume was noted as well as rapid tumor shrinking. Because this patient died despite previous prophylaxic anti-uric acid treatment and hemodialysis, his case illustrates the need to anticipate the development of acute renal failure, even though there may be no remarkable serum uric acid elevation after the initiation of radiotherapy.     

弥漫大B细胞淋巴瘤患者miR-125表达水平与临床病理及预后的关系分析

目的 分析弥漫大B细胞淋巴瘤(Diffuse Large B-cell Lymphoma,DLBCL)患者微小RNA-125(microRNA-125,miR-125)表达水平与临床病理参数及预后的关系.方法 回顾性分析2015年3月-2017年3月四川大学华西医院血液内科收治的148例DLBCL患者的临床资料,列为D...     

化疗中期及终末期18F—FDGPET／CT显像对弥漫性大B细胞淋巴瘤患者预后评估价值

目的探讨化疗中期及终末期18F-FDGPET／CT显像对DLBCL患者预后评估的价值。方法回顾性分析2005年至2011年经手术或活组织病理检查确诊的110例（男62例,女48例,中位年龄52岁）DLBCL患者的18F—FDGPET／CT显像结果。其中在化疗中期（4周期）、化疗终末期（6∽8周期）、化疗中期＋终末期行PET／CT检查的患者分别为42、44和24例。根据显像结果将患者分为阳性组和阴性组,以无进展生存（PFS）期及总体生存（os）期为评价指标,对各组患者进行预后评估。组间PFS率及Os率的比较采用疋。检验,预后因素分析采用Kaplan—Meier生存分析法。结果化疗中期”F—FDGPET／CT显像阳性组28例,阴性组38例,2组中位PFS期分别为20和37个月,3年PFS率分别为17．9％（5／28）和52．6％（20／38）,差异有统计学意义（χ2=8．285,P〈O．01）;中位Os期分别为28和39个月,3年0s率分别为35．7％（10／28）和55．3％（21／38）,差异无统计学意义（χ2=2．473,P〉0．05）。化疗终末期”F．FDGPET／CT显像阳性组20例,阴性组48例,2组中位PFS期分别为21和54个月,3年PFS率分别为20．O％（4／20）和77．1％（37／48）,差异有统计学意义（χ2=19．215,P〈0．01）;中位Os期分别为26和57个月,3年0s率分别为25．0％（5／20）和83．3％（40／48）,差异有统计学意义（χ2=21．462,P〈0．01）。结论化疗终末期PET／CT是DLBCL患者预后评估的可靠方法,而化疗中期PET／CT对患者的预后评估有一定的局限性。     

原发性乳腺弥漫性大B细胞淋巴瘤MRI表现及与病理对照

目的:探讨原发性乳腺弥漫性大B细胞淋巴瘤的MRI表现及其临床病理特征.方法:回顾性分析18例经组织病理学证实的原发性乳腺弥漫性大B细胞淋巴瘤的临床、MRI及病理学特征.结果:18例患者均为女性,平均年龄51岁.临床触及肿块18例,6例在短期内迅速增大.MRI检查共发现病灶25处,其中单发病灶13例,单侧多发病灶2例,双侧多发病灶3例.病灶在T1 WI上呈等或略低信号,T2 WI呈高或稍高信号.增强后呈肿块样强化19处(76.0％),其中形态呈椭圆形或不规则形16处(84.2％),内部均匀强化14处(73.7％);非肿块样强化6处,其中内部不均匀强化3处(50.0％);10处病灶内可见“血管造影征”.伴有皮肤增厚7例,同侧腋窝淋巴结肿大10例.病理学镜下表现为肿瘤性淋巴样细胞较大或中等大小,弥漫性分布,部分呈单行索条状排列.结论:原发性乳腺弥漫性大B细胞淋巴瘤的病理学基础决定了其MRI表现有一定特征性,MRI检查有助于本病的诊断及鉴别诊断.     

Whole-body diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient mapping for staging patients with diffuse large B-cell lymphoma

Objective

To design a whole-body MR protocol using exclusively diffusion-weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with diffuse large B-cell lymphoma (DLBCL), with integrated FDG PET/CT as the reference standard.

Methods

Fifteen patients underwent both whole-body DWI (b?=?50, 400, 800 s/mm²) and PET/CT for pretreatment staging. Lymph node and organ involvement were evaluated by qualitative and quantitative image analysis, including measurement of the mean apparent diffusion coefficient (ADC).

Results

A total of 296 lymph node regions in the 15 patients were analysed. Based on International Working Group size criteria alone, DWI findings matched PET/CT findings in 277 regions (94%) (kappa score?=?0.85, P?<?0.0001), yielding sensitivity and specificity for DWI lymph node involvement detection of 90% and 94%. Combining visual ADC analysis with size measurement increased DWI specificity to 100% with 81% sensitivity. For organ involvement, the two techniques agreed in all 20 recorded organs (100%). All involved organ lesions showed restricted diffusion. Ann Arbor stages agreed in 14 (93%) of the 15 patients.

Conclusion

Whole-body DWI with ADC analysis can potentially be used for lesion detection and staging in patients with DLBCL.     

^18F—FDG PET／CT评价弥漫性大B细胞淋巴瘤化疗中期的治疗反应

目的探讨^18F-FDGPET／CT评价弥漫性大B细胞淋巴瘤（DLBCL）患者化疗中期治疗反应的价值。方法DLBCL初诊患者53例,采用环磷酰胺＋阿霉素＋长春新碱＋泼尼松（CHOP）或利妥苷单克隆抗体＋环磷酰胺＋阿霉素＋长春新碱＋泼尼松（R-CHOP）方案化疗,分别于化疗前和化疗中期（4个疗程后）进行^18F-FDGPET／CT显像。根据肿瘤对化疗的反应将病例分为完全反应组、部分反应组和无反应组,比较3组患者的完全缓解率。用SPSS13．0软件进行统计学分析,完全缓解率的比较用x2检验。结果完全反应组、部分反应组和无反应组的临床完全缓解率分别为88．5％（23／26）、73．3％（11／15）和8．3％（1／12）,3组问差异有统计学意义（X2=23．548,P=0．000）。完全反应组、部分反应组的完全缓解率高于无反应组（X2=22．656,P=0．000和x2=11．407,P=0．001）。结论DLBCL患者化疗中期^18F-FDG PET／CT显像有助于预测其化疗疗效。     

Erythema nodosum associated with diffuse,large B-cell non-Hodgkin lymphoma detected by FDG PET

A patient is described with non-Hodgkin lymphoma and erythematous skin nodules suspected to be erythema nodosum. The patient underwent serial fluorodeoxyglucose (FDG) positron emission tomography (PET), which demonstrated normalization of FDG uptake by the lymphoma after 2 cycles of chemotherapy, but there was new abnormal uptake involving the subcutaneous tissues of the lower extremities. A typical skin lesion was sampled and showed the appearance of erythema nodosum with no evidence of lymphoma. The FDG uptake gradually diminished on serial PET imaging after treatment with nonsteroidal antiinflammatory drugs. In view of the recognized association of erythema nodosum with malignancy and the differential rate of response to chemotherapy, the lesions of erythema nodosum may be a source of a false-positive PET interpretation, and histologic assessment should be considered.     

Collateral circulation is an independent radiological predictor of outcome after thrombolysis in acute ischaemic stroke

We tested the hypothesis that the type of vascular occlusion, recanalisation and collateralisation are predictive of outcome after thrombolytic therapy in acute ischaemic stroke. We carried out angiography and local intra-arterial (97) or systemic (14) thrombolysis within 6 h of the onset in patients with an ischaemic stroke in the territory of the internal carotid artery. Early ischaemic signs (EIS) on pretreatment CT and angiographic findings were classified and analysed in relation to clinical outcome at 3 months. A favourable outcome (Barthel index [BI]>/= 90) was found in 40% of patients with an occlusion of the middle cerebral artery trunk whereas intracranial occlusion of the internal carotid artery ("carotid T occlusion") was followed by death or severe disability (BI<50) in 87%. Significant univariate predictors of favourable outcome were occlusion type ( P<0.01), recanalisation ( P<0.01) and collateralisation ( P<0.01). However, multivariate analysis revealed a significant relationship only between collateralisation and favourable outcome (odds ratio 5.9, 95% confidence interval 1.3-26.7, P=0.02). EIS were not predictive in either case. Occlusion type and recanalisation, are related to outcome only if adequate collateralisation prevents infarction until recanalisation occurs.     

ADC measurements in diffuse large B-cell lymphoma and follicular lymphoma: a DWI and cellularity study

Purpose

Diffusion-weighted magnetic resonance imaging (DW-MRI) allows quantifying the random motion of water molecules in tissue by means of apparent diffusion coefficient (ADC) measurements. The aim of the study was to determine whether ADC measurements allow discrimination of diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL), and to examine the relationship between cellularity and ADC value of the tumor using DWI.

Materials and methods

Thirty-two patients with histologically proven non-Hodgkin lymphoma (21 with DLBCL and 11 with FL, 17 males and 15 females, mean age 62 ± 13 years) underwent conventional MRI and DWI examination before treatment. The ADC values of DLBCL were compared to those of FL. The ADC value of the tumor was also correlated with the tumor tissue cellularity.

Results

The mean ADC value of DLBCL was not significantly different from that of FL (0.70 ± 0.16 × 10⁻³ mm²/s vs. 0.76 ± 0.12 × 10⁻³ mm²/s, P = 0.21). The cellularity of DLBCL was significantly lower than that of FL (2991 ± 351 cells/view vs. 4412 ± 767 cells/view, P < 0.001). There was no correlation between the ADC value and the tissue cellularity of the tumor in patients with DLBCL and FL.

Conclusion

ADC measurements could not differentiate between DLBCL and FL, and there was no correlation between the ADC value and cellularity of the tumor in patients with DLBCL and FL.     

Three cases of diffuse large B-cell lymphoma of the mandible treated with radiotherapy and chemotherapy

CASE REPORT: We report three cases of diffuse large B-cell lymphoma of the mandible and a review of the literature. All 3 of our patients had stage I AE disease and had complete remission for more than 2 years after 42-46 Gy of irradiation to the primary tumor with regional lymph nodes and 3 courses of chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and predonisolone (CHOP). Literature analysis, although biased toward published data, indicated that the 3-year disease-specific survival rates for non-Hodgkin's lymphoma (NHL) of the mandible were 90.5% and 47.6% for stages I and II, respectively. The treatment results for NHL of the mandible may be similar to general primary bone NHL and to other extranodal NHL's. CONCLUSION: Radiotherapy alone is not sufficient for tumor control for stage I+II, disease, and combination chemotherapy may be needed.     

Structured reporting adds clinical value in primary CT staging of diffuse large B-cell lymphoma

Objectives

To evaluate whether template-based structured reports (SRs) add clinical value to primary CT staging in patients with diffuse large B-cell lymphoma (DLBCL) compared to free-text reports (FTRs).

Methods

In this two-centre study SRs and FTRs were acquired for 16 CT examinations. Thirty-two reports were independently scored by four haematologists using a questionnaire addressing completeness of information, structure, guidance for patient management and overall quality. The questionnaire included yes-no, 10-point Likert scale and 5-point scale questions. Altogether 128 completed questionnaires were evaluated. Non-parametric Wilcoxon signed-rank test and McNemar’s test were used for statistical analysis.

Results

SRs contained information on affected organs more often than FTRs (95 % vs. 66 %). More SRs commented on extranodal involvement (91 % vs. 62 %). Sufficient information for Ann-Arbor classification was included in more SRs (89 % vs. 64 %). Information extraction was quicker from SRs (median rating on 10-point Likert scale=9 vs. 6; 7–10 vs. 4–8 interquartile range). SRs had better comprehensibility (9 vs. 7; 8–10 vs. 5–8). Contribution of SRs to clinical decision-making was higher (9 vs. 6; 6–10 vs. 3–8). SRs were of higher quality (p < 0.001). All haematologists preferred SRs over FTRs.

Conclusions

Structured reporting of CT examinations for primary staging in patients with DLBCL adds clinical value compared to FTRs by increasing completeness of reports, facilitating information extraction and improving patient management.

Key Points

? Structured reporting in CT helps clinicians to assess patients with lymphoma. ? This two-centre study showed that structured reporting improves information content and extraction. ? Patient management may be improved by structured reporting. ? Clinicians preferred structured reports over free-text reports.

     

类风湿性关节炎合并弥漫大B细胞淋巴瘤5例并文献复习

目的 探讨类风湿性关节炎(RA)合并弥漫大B细胞淋巴瘤(DLBCL)的临床特点,提高对此类疾病的认识.方法 回顾性分析首都医科大学附属北京世纪坛医院2011年1月-2018年1月住院治疗的RA合并DLBCL患者的临床资料.结果 RA合并DLBCL患者5例,占同期RA住院病例的0.32％(5/1561),其中男1例,女4...     

Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma

Purpose

Interim ¹⁸F-FDG PET performed early during the course of therapy in diffuse large B-cell lymphoma (DLBCL) is a good predictor of outcome. However, interpretation criteria for interim PET for the evaluation of tumour response are still not clearly defined. The study aim was to assess whether interim PET can predict overall survival (OS) and progression-free survival (PFS) in DLBCL patients following three different sets of parameters, two qualitative (visual) methods and one semiquantitative.

Methods

A total of 50 newly diagnosed DLBCL patients were prospectively enrolled in this study. All patients had a PET/CT scan at diagnosis and an interim PET/CT scan after the second or third cycle of chemotherapy. Three methods of evaluation for the interim PET/CT were used: a qualitative three-point scoring (3-PS) method, a qualitative 5-PS method and a semiquantitative method (ΔSUV_max). The degree of correlation between therapy response seen on FDG PET and PFS and OS was determined.

Results

The analysis of the visual 3-PS method showed no statistically significant difference in PFS and OS. The estimated 5-year PFS and OS were 79 % and 92 %, respectively, in patients with an interim PET scan showing uptake not greater than in the liver versus 50 % in patients with uptake greater than in the liver, and this difference was statistically significant. The optimal cut-off value of ΔSUV_max that could predict the PFS and OS difference in patients with DLBCL was 76 % (95 % CI 62.7–89.2 %) and 75 % (95 % CI, 54.6–95.4 %), respectively.

Conclusion

Our results support the use of liver uptake as an indicator in the qualitative evaluation of interim PET, or a ΔSUV_max greater than 75 % in semiquantitative analysis. Interim PET may predict PFS and OS and could be considered in the prognostic evaluation of DLBCL.