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.     

PET/CT与临床预后因素在弥漫大B细胞淋巴瘤疗效评价及预后评估中的应用

弥漫大B细胞淋巴瘤（DLBCL）是最常见的侵袭性非霍奇金淋巴瘤（NHL）。应用美罗华联合环磷酰胺、阿霉素、长春新碱、甲泼尼龙化疗方案后,DLBCL患者的治愈率可达60%~80%。由于DLBCL在分子病理等方面具有明显的异质性,不同患者的疗效和预后不同,因此如何正确评价其疗效及预后是目前研究的热点。18F-FDG PET/CT是DLBCL患者常用的疗效评价及预后评估的影像学工具。国际预测预后指数（IPI）以及美国国立综合癌症网络-国际预后指标（NCCN-IPI）是广泛应用于临床的恶性淋巴瘤预后评分系统。近年来,一些新的临床及分子病理因素的预后价值也先后被探索。笔者将对PET/CT、临床预后评分系统、不同的临床及分子病理预后因素在DLBCL患者的疗效评价及预后评估中的应用、研究进展以及发展趋势进行综述。     

Recurrent renal cell carcinoma: clinical and prognostic value of FDG PET/CT

Purpose

The purpose of our study was 1) to evaluate the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 2) to assess the impact of FDG PET/CT on treatment decision-making, and 3) to estimate the prognostic value of FDG PET/CT in the restaging process among patients with renal cell carcinoma (RCC).

Methods

From the FDG PET/CT databases of San Raffaele Hospital in Milan, Italy, and the Veneto Institute of Oncology in Padua, Italy, we selected 104 patients with a certain diagnosis of RCC after surgery, and for whom at least 24 months of post-surgical FDG PET/CT, clinical, and instrumental follow-up data was available. The sensitivity and specificity of FDG PET/CT were assessed by histology and/or other imaging as standard of reference. Progression-free survival (PFS) and overall survival (OS) were computed using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to identify predictors of outcome.

Results

FDG PET/CT resulted in a positive diagnosis in 58 patients and a negative diagnosis in 46 patients. Sensitivity and specificity were 74 % and 80 %, respectively. FDG PET/CT findings influenced therapeutic management in 45/104 cases (43 %). After a median follow-up period of 37 months (± standard deviation 12.9), 51 (49 %) patients had recurrence of disease, and 26 (25 %) had died. In analysis of OS, positive versus negative FDG PET/CT was associated with worse cumulative survival rates over a 5-year period (19 % vs. 69 %, respectively; p <0.05). Similarly, a positive FDG PET/CT correlated with a lower 3-year PFS rate. In addition, univariate and multivariate analysis revealed that a positive scan, alone or in combination with disease stage III–IV or nuclear grading 3–4, was associated with high risk of progression (multivariate analysis = hazard ratios [HRs] of 4.01, 3.7, and 2.8, respectively; all p?<?0.05).

Conclusions

FDG PET/CT is a valuable tool both in treatment decision-making and for predicting survival and progression in patients affected by RCC.

     

18F-FDG PET/CT联合改良国际预后指标(NCCN-IPI)对弥漫大B细胞淋巴瘤预后评估的价值分析

目的 探讨改良国际预后指标（NCCN-IPI）对治疗结束后18F-FDG PET/CT评价为阴性的弥漫大B细胞淋巴瘤（DLBCL）患者的预后分层价值。 方法 回顾性分析2013年4月至2017年8月在苏州大学附属第一医院经过6~8周期R-CHOP类方案化疗后,并经18F-FDG PET/CT评价为阴性的60例DLBCL患者的临床资料,其中男性28例、女性32例,中位年龄51岁（16~81岁）。采用NCCN-IPI进行危险度分层,采用 Log-rank 检验比较各组间无进展生存（PFS）期和总生存（OS）期的差异。 结果 所有患者2年PFS率为83.33%（50/60）,2年OS率为96.67%（58/60）。根据NCCN-IPI评分,低危组占35.0%（21/60）,低中危组占41.7%（25/60）,中高危组占18.3%（11/60）,高危组占5.0%（3/60）。低危组与其他组间PFS差异有统计学意义（P=0.0272、0.0143、<0.0001）,高危组与其他组间OS差异有统计学意义（P=0.0098、0.0166、0.0045）,余各组间PFS及OS差异无统计学意义（均P>0.05）。 结论 应用NCCN-IPI可以对治疗结束后18F-FDG PET/CT评价为阴性的DLBCL患者进行进一步的预后分层。     

18F-FDG PET/CT在弥漫性大B细胞淋巴瘤疗效评价中的临床价值

目的 探讨18F-FDG PET/CT在弥漫性大B细胞淋巴瘤（DLBCL）化疗早期及化疗后疗效评价中的临床价值。 方法 回顾性分析采用美罗华联合环磷酰胺+多柔比星+长春新碱+泼尼松方案或环磷酰胺+多柔比星+长春新碱+泼尼松方案化疗的34例DLBCL患者的PET/CT结果。所有患者分别在化疗前、化疗6疗程后行PET/CT,比较化疗前后病灶最大标准化摄取值（SUV_max）及病灶最大直径（D_max）;其中12例患者于化疗前、第2疗程结束后、第4疗程结束后行PET/CT,比较3组间的SUV_max与D_max。对在化疗6疗程后行PET/CT显像已达到完全缓解的8例和部分缓解的10例患者进行临床随访,观察1年无进展生存期（PFS）。 结果 ①34例患者化疗前和6疗程化疗后,SUV_max之间和D_max之间的差异均有统计学意义（t=3.58和2.96,P均 < 0.05）。② 12例患者在化疗前、第2疗程结束后、第4疗程结束后,SUV_max之间和D_max之间的差异均有统计学意义（F=18.64和4.33,P均 < 0.05）;第2疗程结束后与化疗前相比,病灶D_max未见显著变化（t=1.05,P > 0.05）,SUV_max显著降低（t=5.37,P < 0.05）;第4疗程结束后与化疗前相比,SUV_max之间和D_max之间的差异均具有统计学意义（t=8.56和3.90,P均 < 0.05）。③对18例患者进行的随访发现,完全缓解的8例中,PFS > 1年者6例,PFS < 1年者2例;部分缓解的10例中,PFS > 1年者2例,PFS < 1年者8例。 结论 在DLBCL化疗早期及化疗后的疗效评价上,PET比CT更灵敏,以两种显像方法相结合的PET/CT在淋巴瘤疗效评价上具有较高的临床价值。     

弥漫性大B细胞淋巴瘤预后因素研究进展

弥漫性大B细胞淋巴瘤（DLBCL）是最常见的侵袭性非霍奇金B细胞淋巴瘤,具有高度异质性,识别高危患者尤为重要,目前已经发现多种因素影响其预后。笔者根据国内外的研究进展,从临床特征、分子生物学特征和PET/CT多方面对影响DLBCL患者预后的因素进行综述。     

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。     

18F-FDG PET/CT在鼻咽癌中的诊断价值

目的 探讨18F-FDG PET/CT在鼻咽癌中的诊断价值.方法 回顾性分析我院2007年3月～2010年3月以鼻咽部肿块就诊的36例患者资料,所有患者均行鼻咽部18F-FDG PET/CT检查及鼻内镜下取材病检确诊.结果 24例病检后确诊为鼻咽癌患者,18F-FDG PET/CT检查均为局限性高代谢灶;12例病检后确诊为鼻咽部炎性肿块患者中,8例18F-FDG PET/CT检查均为鼻咽部局限性低代谢灶,考虑炎症,有4例18F-FDG PET/CT检查为鼻咽部局限性高代谢灶,误诊为鼻咽癌.结论 18F-FDG PET/CT检查是诊断鼻咽癌的较好方法,结合患者临床症状,可以为鼻咽部肿块的良恶性鉴别提供可靠依据.     

Diagnostic and prognostic impact of 18F-FDG PET/CT in follicular lymphoma

Purpose

The aim of this study was to assess the usefulness of positron emission tomography/computed tomography in staging, prognosis evaluation and restaging of patients with follicular lymphoma.

Methods

A retrospective study was performed on 45 patients with untreated biopsy-proven follicular lymphoma who underwent ¹⁸F-fluorodeoxyglucose PET/CT (FDG PET/CT) and CT before and after chemoimmunotherapy induction treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone).

Results

PET/CT detected more nodal (+51%) and extranodal (+89%) lesions than CT. PET/CT modified Ann Arbor staging in eight patients (18%). Five patients (11%) initially considered as being early stage (I/II) were eventually treated as advanced stage (III/IV). In this study, an initial PET/CT prognostic score was significantly more accurate than the Follicular Lymphoma International Prognostic Index score in identifying patients with poor prognosis (i.e. patients with incomplete therapeutic response or early relapse). The accuracy of PET/CT for therapeutic response assessment was higher than that of CT (0.97 vs 0.64), especially due to its ability to identify inactive residual masses. In addition, post-treatment PET/CT was able to predict patients’ outcomes. The median progression-free survival was 48 months in the PET/CT-negative group as compared with 17.2 months for the group with residual uptake (p?<?10^?4).

Conclusion

FDG PET/CT is useful for staging and assessing the prognosis and therapeutic response of patients with follicular lymphoma.     

Current role of FDG PET/CT in lymphoma

The management approach in Hodgkin’s (HL) and high-grade non-Hodgkin’s lymphomas (NHL) has shifted towards reducing the toxicity and long-term adverse effects associated with treatment while maintaining favorable outcomes in low-risk patients. The success of an individualized treatment strategy depends largely on accurate diagnostic tests both at staging and during therapy. In this regard, positron emission tomography (PET) using fluorodeoxyglucose (FDG) with computed tomography (CT) has proved effective as a metabolic imaging tool with compelling evidence supporting its superiority over conventional modalities, particularly in staging and early evaluation of response. Eventually, this modality was integrated into the routine staging and restaging algorithm of lymphomas. This review will summarize the data on the proven and potential utility of PET/CT imaging for staging, response assessment, and restaging, describing current limitations of this imaging modality.     

FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis

Purpose

To systematically review and meta-analyse published data on the diagnostic performance of ¹⁸F-FDG PET/CT in detecting bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Methods

PubMed/MEDLINE and Embase were systematically searched for relevant studies. The methodological quality of each study was assessed. Sensitivities and specificities of FDG PET/CT in individual studies were calculated and meta-analysed with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted summary proportions of discrepancies between the FDG PET/CT and (blind) bone marrow biopsy (BMB) results among all patients were calculated.

Results

Seven studies, with a total of 654 patients with newly diagnosed DLBCL, were included. Overall, the quality of the included studies was moderate. The sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8 % to 95.8 % and from 99.0 % to 100 %, with pooled estimates of 88.7 % (95 % confidence interval, CI, 82.5 – 93.3 %) and 99.8 % (95 % CI 98.8 – 100 %), respectively. The area under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT-negative patients with positive BMB findings among all patients was 3.1 % (95 % CI 1.8 – 5.0 %) and the weighted summary proportion of FDG PET/CT-positive patients with negative BMB findings among all patients was 12.5 % (95 % CI 8.4 – 17.3 %).

Conclusion

FDG PET/CT is accurate and complementary to BMB for detecting bone marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT scan cannot rule out the presence of bone marrow involvement, but positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in these patients.     

FDG PET/CT predictive role in follicular lymphoma

Purpose  

We present findings concerning ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) at end-treatment evaluation in follicular lymphoma (FL) in order to establish possible predictive factors for progression-free survival (PFS) and patient outcome.     

Nonossifying fibroma can mimic residual lymphoma in FDG PET: additional value of combined PET/CT

A 12-year-old girl was diagnosed with Hodgkin's lymphoma and underwent conventional cross-sectional imaging for initial staging. Chemotherapy was given according to standard pediatric protocols. At the end of therapy, an F-18 FDG PET/CT examination was performed to evaluate the therapeutic response. The scan demonstrated focal uptake of FDG in the right distal femur and residual lymphoma was taken into consideration. However, findings in the coregistered CT scan were consistent with nonossfiying fibroma, a common benign skeletal lesion. Combined PET/CT imaging can be helpful to identify benign bone lesions mimicking metastatic or residual disease in F-18 FDG PET as illustrated by this case.     

FDG avidity and PET/CT patterns in primary gastric lymphoma

PURPOSE: The use of 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in primary gastric lymphoma (PGL) is challenging due to physiologic FDG activity in the stomach and variability in the degree of uptake in various histologic subtypes. This study assesses FDG avidity and PET/CT patterns in newly diagnosed PGL. METHODS: Sixty-two PET/CT studies of newly diagnosed PGL were reviewed (24 low-grade mucosa-associated lymphoid tissue [MALT], 38 aggressive non-Hodgkin's lymphoma [AGNHL]). FDG avidity, patterns (focal/diffuse), and intensity (visually vs. the liver and SUVmax) were assessed and compared to 27 controls. Gastric CT abnormalities and extragastric sites were recorded. RESULTS: Gastric FDG uptake was found in 55/62 (89%) PGL (71% MALT vs. 100% AGNHL, p < 0.001) and 63% controls. A diffuse pattern was found in 60% PGL (76% MALT vs. 53% AGNHL, p = NS) and 47% controls. FDG uptake higher than liver was found in 82% PGL (58% MALT vs. 97% AGNHL, p < 0.05) and 63% controls. SUVmax in FDG-avid PGLs was 15.3 +/- 11.7 (5.4 +/- 2.9 MALT vs. 19.7 +/- 11.5 AGNHL, p < 0.001) and 4.6 +/- 1.4 in controls. CT abnormalities were found in 79% PGL (thickening, n = 49; ulcerations, n = 22). Extra-gastric FDG-avid sites were seen in none of MALT, but 61% of AGNHL (nodal, n = 18; nodal and extranodal, n = 5). CONCLUSIONS: FDG avidity was present in 89% of PGLs, including all patients with AGNHL but only 71% of MALT. FDG uptake can be differentiated, in particular in AGNHL-PGL, from physiologic tracer activity by intensity but not by pattern. Extragastric foci on PET and structural CT abnormalities are additional parameters that can improve PET/CT assessment of PGL. Defining FDG avidity and PET/CT patterns in AGNHL and a subgroup of MALT-PGL before treatment may be important for further monitoring therapy response.     

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma

Aim

The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of ¹⁸F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT).

Materials and methods

From the databases of two centers including 31,500 ¹⁸F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent ¹⁸F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted ¹⁸F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables.

Results

Recurrent GCT was confirmed in 47 of 52 patients with pathological ¹⁸F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of ¹⁸FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively.¹⁸F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from “wait and watch” to new chemotherapy in six patients and the “wait-and-watch” approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological ¹⁸F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological ¹⁸F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological ¹⁸F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. ¹⁸F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003).

Conclusion

¹⁸F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, ¹⁸F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process.