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.     

Predictive and prognostic value of metabolic tumour volume and total lesion glycolysis in solid tumours

Data available in patients suffering from squamous cell carcinoma of the head and neck, lung carcinoma, oesophageal carcinoma and gynaecological malignancies suggest that metabolic tumour volume and to a lesser extent total lesion glycolysis have the potential to become valuable in the imaging of human solid tumours as prognostic biomarkers for short- to intermediate-term survival outcomes, adding value to clinical staging, for assessment of response to treatment with neoadjuvant and concurrent chemotherapy, and for treatment optimization; for example, based on early treatment response assessment using changes in metabolic tumour volume over time, it might be possible to select patients who require a more aggressive treatment to improve their outcome. Prospective studies enrolling consecutive patients, adopting standardized protocols for FDG PET acquisition and processing, adjusting for potential confounders in the analysis (tumour size and origin) and determining the optimal methodology for determination of these novel markers are mandatory.     

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.

     

Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

Purpose

We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL).

Methods

TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent ¹⁸F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS).

Results

Median follow-up was 39 months. Average pretherapy TMTV was 509?±?568 cm³. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm³) and 60 % in the high metabolic burden group (TMTV >550 cm³, p?=?0.04), and prediction of OS was even better (87 % vs. 60 %, p?=?0.0003). Cox regression showed independence of TMTV for OS prediction (p?=?0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index.

Conclusion

Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL.     

Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on 18F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma

Purpose

The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment ¹⁸F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL).

Methods

We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment ¹⁸F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV?>?3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG).

Results

During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm³ and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS.

Conclusion

Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes.     

Analyses of patterns-of-failure and prognostic factors according to radiation fields in early-stage Hodgkin lymphoma

Purpose

Doses and volumes of radiation therapy (RT) for early stages of Hodgkin lymphoma (HL) have been reduced over the last 30 years. Combined modality therapy (CMT) is currently the standard treatment for most patients with early-stage HL. The aim of this study was to analyze the site of relapse after RT according to the extent of radiation fields.

Patients and methods

Between 1987 and 2011, 427 patients were treated at our institution with RT ± chemotherapy for stage-I/II HL. Among these, 65 patients who experienced a relapse were retrospectively analyzed. Most patients had nodular sclerosis histology (86?%) and stage-II disease (75.9?%). Bulky disease was present in 21?% and 56?% of patients belonged to the unfavorable risk group according to European Organization for Research and Treatment of Cancer (EORTC)/The Lymphoma Study Association (LYSA) definitions. CMT was delivered to 91?% of patients. All patients received RT with doses ranging from 20 to 45 Gy (mean = 34 ± 5.3 Gy). The involved-field RT technique was used in 59?% of patients.

Results

The mean time between diagnosis and relapse was 4.2 years (range 0.3–24.5). Out-of-field relapses were suffered by 53?% of patients. Relapses occurred more frequently at out-of-field sites in patients with a favorable disease status, whereas in-field relapses were associated with bulky mediastinal disease. Relapses occurred later for favorable compared with the unfavorable risk group (3.5 vs. 2.9 years, p = 0.5). From multivariate analyses, neither RT dose nor RT field size were predictive for an in-field relapse (p = 0.25 and p = 0.8, respectively), only bulky disease was predictive (p = 0.018).

Conclusion

In patients with bulky disease, RT dose and RT field size were not predictive for an in-field relapse. In this subgroup of patients, chemotherapy should be intensified. We confirmed the bad prognosis of early relapses.

     

影像学技术在霍奇金淋巴瘤诊疗中的价值

在我国,霍奇金淋巴瘤（HL）占全部恶性淋巴瘤的10.9％,约90％起源于淋巴结,通常呈对称性淋巴结肿大,很少累及结外组织.HL对放疗、化疗很敏感,是可治愈的肿瘤之一.该文主要就CT成像、MRI、67Ga成像、PET或PET/CT在HL诊断及预后评估等方面的应用作一综述,以进一步提高对HL影像学表现及其临床应用的认识.     

Asphericity of pretherapeutic tumour FDG uptake provides independent prognostic value in head-and-neck cancer

Objective

To propose a novel measure, namely the ‘asphericity’ (ASP), of spatial irregularity of FDG uptake in the primary tumour as a prognostic marker in head-and-neck cancer.

Methods

PET/CT was performed in 52 patients (first presentation, n?=?36; recurrence, n?=?16). The primary tumour was segmented based on thresholding at the volume-reproducible intensity threshold after subtraction of the local background. ASP was used to characterise the deviation of the tumour’s shape from sphere symmetry. Tumour stage, tumour localisation, lymph node metastases, distant metastases, SUV_max, SUV_mean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were also considered. The association of overall (OAS) and progression-free survival (PFS) with these parameters was analysed.

Results

Cox regression revealed high SUV_max [hazard ratio (HR)?=?4.4/7.4], MTV (HR?=?4.6/5.7), TLG (HR?=?4.8/8.9) and ASP (HR?=?7.8/7.4) as significant predictors with respect to PFS/OAS in case of first tumour manifestation. The combination of high MTV and ASP showed very high HRs of 22.7 for PFS and 13.2 for OAS. In case of recurrence, MTV (HR?=?3.7) and the combination of MTV/ASP (HR?=?4.2) were significant predictors of PFS.

Conclusions

ASP of pretherapeutic FDG uptake in the primary tumour improves the prediction of tumour progression in head-and-neck cancer at first tumour presentation.

Key Points

?Asphericity (ASP) characterises the spatial heterogeneity of FDG uptake in tumours ? ASP is a promising prognostic parameter in head-and-neck cancer ? ASP is useful for identification of high-risk patients with head-and-neck cancer     

Interim FDG-PET/CT in Hodgkin lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET)

Objective

To evaluate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with Hodgkin lymphoma (HL) undergoing interim FDG-PET/CT and to compare rPET with the 5-point Deauville Score (5p-DS).

Methods

Sixty-eight patients with HL undergoing interim FDG-PET/CT after first courses of chemotherapy were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cutpoint of rPET with respect to progression free survival (PFS). The prognostic significance of rPET was compared with 5p-DS (scores 4 and 5 considered as positive). Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of an adverse event as the gold standard.

Results

The ROC analysis for rPET as a predictor of progression showed an optimal rPET cutpoint of 1.14. Both 5p-DS and rPET were strong outcome predictors (p < 0.001). Patients with negative 5p-DS and patients with rPET <1.14 had a similar two-year PFS (86 and 87 %, respectively). Patients with a positive 5p-DS had a 2-year PFS of 27 %, while patients with rPET >1.14 had a 2-year PFS of 15 %. 5p-DS and rPET cutoff of 1.14 showed a PPV of 58 versus 70 %, and a NPV of 85 versus 86 %, respectively.

Conclusions

rPET could be considered an accurate prognostic factor in patients with HL undergoing interim FDG-PET/CT. Larger prospective studies are needed to confirm these data.

     

FDG PET／CT代谢体积对食管癌术后预后的预测价值

目的研究食管癌患者^18F-FDG PET／CTMTV与预后的关系。方法回顾性分析2004年3月至2008年3月行^18F—FDG PET／CT检查的49例Ⅰ—Ⅳa期的食管癌患者,均经病理检查证实,随访资料完整。患者均行食管癌切除术,随访截止至2009年11月,中位随访时间为29（8～57）个月。应用Kaplan—Meier法及Cox比例风险模型分析年龄、性别、肿瘤位置、肿瘤组织分化程度、PET／CT示肿瘤长径、美国肿瘤联合会（AJCC）分期、转移淋巴结个数、原发灶SUVmax及MTV与预后的关系。结果在单因素分析中,仅AJCC分期[χ^2=16．206,危险比（HR）=1．177,P〈0．001）,淋巴结分期（N）（χ^2=9．536,HR=10．833,P=0．002）,浸润深度（T）（χ^2=5．810,FIR=2．397,P=0．016）,淋巴结转移个数（χ^2=11．423,HR=1．567,P=0．001）、MTV（χ^2=3．872,HR=2．433,P=0．049）对预后存在预测作用。对以上变量行多因素分析,仅AJCC分期及MTV是独立的预后因子（r=4．525,HR=1．170,P=0．033;χ^2=4．875,HR=3．071,P=0．027）。Kaplan-Meier生存分析显示术前低MTV组比高MTV组的生存率高（Log—rank检验,χ^2=4．186,P=0．041）。结论MTV与食管癌术后患者的预后密切相关。对于高MTV患者,术后可能需要接受更加积极的治疗。     

Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG PET/CT in anal canal cancer

Purpose

The aim of this study was to confirm the prognostic value of metabolic tumour volume (MTV) at the primary site on initial work-up FDG PET/CT in patients with squamous cell carcinoma (SCC) of the anal canal.

Methods

Patients with a recent diagnosis of SCC of the anal canal without metastases undergoing PET/CT for initial work-up and treated with (chemo)radiotherapy were retrospectively reviewed. Computer-aided MTV and SUVmax were determined. Survival rates were estimated using the Kaplan-Meier method. Cox regression analysis was used to evaluate prognostic variables of progression-free survival and overall survival (OS).

Results

The study group comprised 75 patients who had an initial work-up PET/CT. Five patients (6.7 %) had stage I disease, 22 (29.3 %) stage II disease, 20 (26.7 %) stage IIIA disease, and 28 (37.3 %) stage IIIB disease. Median follow-up was 51 months (range 10 – 117 months). Global 4-year OS was 82.7 %, ranging from 100 % in patients with stage I disease to 75 % in patients with stage IIIB disease. MTV at the primary site was significantly and independently correlated with OS (p?<?0.05), as patients with MTV less than 7 cm³ had a better prognosis. SUVmax was not correlated with survival parameters. Metabolic involvement of the inguinal lymph nodes was also correlated with a poor outcome in the univariate analysis (p?<?0.05).

Conclusion

MTV at the primary site is a prognostic biomarker in anal canal cancer. Hypermetabolic inguinal lymph nodes also appear to be correlated with survival.

     

Oesophageal squamous cell carcinoma: relationship between fluorine-18 fludeoxyglucose positron emission tomography CT maximum standardised uptake value, metabolic tumour volume, and tumour, node and metastasis classification

Objectives

We aimed to evaluate the relationships between primary tumour, maximum standardised uptake value, metabolic tumour volume and seventh edition American Joint Committee on Cancer (AJCC) classification in oesophageal squamous cell carcinoma (OSCC) patients.

Methods

Fluorine-18 fludeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)-CT scans of 41 consecutive newly diagnosed OSCC patients were retrospectively reviewed. Maximum standard uptake value (SUV_max) and metabolic tumour volume (MTV) were recorded. Two-tailed Spearman''s correlation was used to analyse the relationships between the metabolic parameters and the AJCC staging system.

Results

Positive correlations were observed between SUV_max, MTV and tumour (T) stage, in addition to node (N) stage and AJCC stage. Both metabolic parameters were independent variables that significantly affected the N stage and AJCC stage, and SUV_max was the only independent variable that significantly affected the T stage.

Conclusion

The metabolic parameters derived from ¹⁸F-FDG PET-CT were positively correlated with T, N and AJCC stage in primary OSCC. Our findings may suggest a complementary role of these parameters to seventh-edition AJCC staging in the prognostication of OSCC patients.Oesophageal cancer is the fifth leading cause of cancer-related mortality in men worldwide. China bore more than half of the global burden of oesophageal squamous cell carcinoma (OSCC) as the dominant type, with a constituent ratio of approximately 90–95% [1]. The tumour size (T), nodal status (N) and distant metastasis (M) system (TNM) of classification for oesophageal cancer by the International Union Against Cancer (UICC) is commonly used in unifying clinicopathological classification, guiding treatment decision making, evaluating prognosis and comparing curative effect. In 2009, the UICC and American Joint Committee on Cancer (AJCC) jointly published the seventh edition of TNM classification of oesophageal malignant tumours according to histological type (squamous or adenocarcinoma), respectively [2]. Tumour metabolic phenotype as a potential prognosticator, however, was not considered [3-5].Maximum standardised uptake value (SUV_max), a semi-quantitative parameter in fused fluorine-18 fludeoxyglucose positron emission tomography-CT (¹⁸F-FDG PET-CT), is known to be a significant factor for locoregional invasion, prognosis and treatment guidance in many malignancies [6-10]. Metabolic tumour volume (MTV), defined as the volume of tumour tissues with increased FDG uptake, is a novel index in ¹⁸F-FDG PET-CT and is the least-studied factor to date. FDG target volume in previous studies was calculated mostly by visual delineation of tumour edge or side-by-side analysis with contrast-enhanced CT scan. On the other hand, MTV in this study was semi-quantitatively measured from attenuation-corrected PET-CT images by using a contouring program, which renders the volume measurement more feasible.To our knowledge, although there was a report discussing the relationship between SUV_max, MTV and the TNM staging in nasopharyngeal carcinoma, few studies to date have examined the relationship in OSCC [11]. Because these quantitative PET parameters also reflect tumour aggressiveness, they may serve as an adjunct to disease staging by characterising the metabolic phenotype of tumours. In this study, we analyse the relationship between SUV_max and MTV of the primary tumour, and TNM classification in patient OSCC without pre-operative therapy.     

18F-FDG PET-CT在霍奇金淋巴瘤疗效评价中的临床价值

目的 探讨18F-FDG PET-CT在霍奇金淋巴瘤(HL)疗效评价中的临床价值.方法 回顾性分析31例HL患者化疗后的18F-FDG PET-CT图像资料,最终结果经病理和临床随访证实,并与治疗后单纯CT结果进行对比分析,采用四格表x2进行差异的显著性检验.结果 ①31例患者共发现病灶145处,其中恶性94处、良性51处.18F-FDG PET-CT评价HL治疗效果的灵敏度、特异度、阳性预测值、阴性预测值及准确率分别为97.87％、94.12％、96.84％、96.00％和96.55％,均明显优于单纯CT检查(x2=9.83、13.49、11.50、11.69、22.58,P均＜0.05).②31例患者经PET-CT显像后,16例(51.61％)更改治疗方案.结论 18F-FDG PET-CT是HL疗效监测的有效手段.     

The spleen in Hodgkin disease: diagnostic value of CT

Findings of CT of the spleen were compared with those of histologic examination in 35 patients who had Hodgkin disease. CT provides a simple way to calculate splenic size. This index is also of value in the assessment of the histologic state of the spleen. An accuracy rate of 91%, specificity of 94%, and a sensitivity of 89% in diagnosing splenic localization of lymphoma was found in this study.