Tommaso Carfagno

Assessment of response to chemoradiation therapy in rectal cancer using MR volumetry based on diffusion-weighted data sets: a preliminary report

PurposeThis study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (VDWI) and compared it with conventional T2-weighted volumetry (VC) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT).Materials and methodsFourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate VC. A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm2 and volume (VDWI) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen.ResultsInterobserver agreement was 0.977 [(95% confidence interval (CI) 0.954–0.989) and 0.956 (95% CI 0.905–0.980) for VC and VDWI and 0.964 (95% CI 0.896–0.988) and 0.271 (95% CI-0.267 to 0.686) between VC and VDWI before and after CHRT. The correlation between TRG and VC and VDWI was, respectively, rho = 0.597 (p<0.05) and r2=0.156 (p=0.162) and rho=0.847 (p<0.001).ConclusionsVDWI seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value.RiassuntoObiettivoScopo del nostro lavoro è stato valutare la fattibilità della volumetria in risonanza magnetica (RM) con immagini pesate in diffusione (VDWI) e confrontare tale metodo con la volumetria convenzionale (VC) basata su immagini T2-pesate in pazienti affetti da neoplasia rettale trattati con chemio-radioterapia (CHRT).Materiali e metodiQuattordici pazienti affetti da neoplasia rettale documentata istologicamente sono stati esaminati con RM prima e dopo chemio-radioterapia. Due osservatori hanno estrapolato indipendentemente il VC dalle immagini T2-pesate e il VDWI dall’acquisizione spin echo (SE)-echo-planar imaging (EPI)-diffusion-weighted (DW) (b-value 800 s/mm2) mediante segmentazione semiautomatica dell’iperintensità patologica. Le due volumetrie sono state comparate e correlate al grado di regressione tumorale sul pezzo operatorio (tumor regression grade, TRG).RisultatiL’accordo inter-osservatore per VC e VDWI è stato di 0,977 (95% intervallo di confidenza 0,954–0,989) e 0,956 (95% intervallo di confidenza 0,905–0,980) e tra VC e VDWI pre- e post-CHRT di 0,964 (95% intervallo di confidenza 0,896–0,988) e 0,271 (95% intervallo di confidenza −0,267–0,686). La correlazione tra TRG e VC e VDWI è stata rispettivamente di rho=0,597 (p<0,05) e rho=0,847 (p<0,001).ConclusioniLa VDWI sembra essere promettente per valutare la risposta alla CHRT nelle neoplasie rettali, tuttavia sono necessari ulteriori studi su casistiche più ampie al fine di migliorare la qualità di tale metodo e per valutarne il reale valore predittivo.

Phase Ib study of poly-epitope peptide vaccination to thymidylate synthase (TSPP) and GOLFIG chemo-immunotherapy for treatment of metastatic colorectal cancer patients

ABSTRACT Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5′-fluorouracil (5′-FU) target. TSPP/VAC1 is a multi-arm trial phase-Ib trial program aimed to investigate the toxicity and biomodulatory activity of a poly-epitope-peptide vaccine to TS (TSPP) in cancer patients (pts). Here, we present the results of the TSPP/VAC1/arm C trial aimed to evaluate TSPP in combination with chemo-immunotherapy in pretreated metastatic colo-rectal cancer (mCRC) pts. Twenty-nine pts, 14 males and 15 females, received poly-chemotherapy with gemcitabine [GEM; 1,000 mg/sqm, day-1], oxaliplatin [OX; 80 mg/sqm, day-2], levofolinate [100 mg/sqm, days 1–2], bolus/infusional 5′-FU [400 mg/800 mg/sqm, days 1–2], sargramostim [50 μg, days 3–7/q30], and interleukin-2 [sc. 0.5 MIU twice a day, days 8–14/18–30] [GOLFIG-regimen]. Seventeen pts received sc. TSPP injections at escalating dosage [3 pts, 100 µg (DL-1); 3 pts, 200 µg (DL-2) and 11pts, 300 µg (DL-3)] one week after each chemotherapy cycle (concomitant module), while 10 out 12 pts received TSPP (300 µg) after 12 GOLFIG courses [dose level (DL)-0] (sequential module). TSPP MTD was not achieved. Adverse events consisted in swelling/erythema at injection sites (17 cases), G1–2 haematological (16 cases) and gastro-enteric events (12), fever, rhinitis, conjunctivitis, and poly-arthralgia and rise in auto-antibodies [ANA, ENA, c-ANCA, p-ANCA in the DL1–3 pts]. Both treatment-modules showed immunomodulating and antitumor activity (disease-control-rate, DL1–3 and DL0 were 70.6% and 83.3%, respectively) with a better survival recorded in the second group [median OS DL1–3 vs. DL0 = 8 vs. 16 mo, p = 0.049]. The promising long-term survival produced by the sequential treatment module deserves further phase II evaluation.

Diffusion-weighted MR Volumetry for Assessing the Response of Rectal Cancer to Combined Radiation Therapy with Chemotherapy

Editor: In the study by Curvo-Semedo and colleagues (1), which appeared in the September 2011 issue of Radiology, the utility of tumor volumetry derived from diffusion-weighted (DW) magnetic resonance (MR) images was evaluated in the assessment of patients with rectal cancer after preoperative combined radiation therapy with chemotherapy (CRT). They showed that post-CRT DW volumetry and volume shrinkage at both T2-weighted and DW MR imaging were highly accurate in the determination of complete response (areas under the receiver operating characteristic curve [AUC] of 0.93, 0.84, and 0.92, respectively). The apparent diffusion coefficient (ADC) and ADC modification rate were not accurate (AUC, 0.54 and 0.51, respectively). The intraclass correlation coefficient (ICC) between T2-weighted and DW MR volumetry was good for pre-CRT measurements but unsatisfactory for post-CRT measurements. This last observation might be attributable to post-CRT fibrosis, which affects the reliability of segmentation of tumor volume on T2-weighted images with respect to post-CRT DW volumetry based on ADC maps (1). In their study, Curvo-Semedo and colleagues defined complete response as tumor regression grade 1 (2) at pathologic examination or a relapsefree follow-up of 17 months. The preliminary results of our study (3), performed with DW imaging using a b value of 800 sec/mm2, are consistent with those reported by Curvo-Semedo and colleagues. In our study of 21 patients who underwent surgical resection after CRT, the interobserver agreement was good (ICC = 0.948 for T2-weighted MR volumetry and 0.916 for DW MR volumetry), whereas the preand post-CRT DW and T2-weighted volumetry concordance consisted of ICC values of 0.828 and 0.151, respectively. The volume segmented from the DW data set on the basis of hyperintensity of hypercellular tissue on DW images showed a good correlation with tumor regression grade (r = 0.556, P , .05). However, DW MR volumetry has some drawbacks, including the difficulty in detecting small neoplastic residual tumors on the post-CRT ADC maps and T2 shinethrough artifacts, owing to necrosis or mucin, which can produce overestimation of residual tumor at the only qualitative eval uation of DW images. These limitations, in our experience, make it difficult to differentiate between patients with tumor regression grades of 1 or 2 (Mandard five-point scale). The relationship to DW MR volumetry of the nodal stage evaluation could increase its prognostic relevance because good prognosis has been demonstrated for low tumor regression grades ypN2 with respect to ypN+ (4). DW MR volumetry seems to be a promising tool for assessing response after preoperative CRT and deserves further study.

Diffusion-Weighted Magnetic Resonance Diagnosis of Local Recurrences of Prostate Cancer after Radical Prostatectomy: Preliminary Evaluation on Twenty-Seven Cases

Objectives. To assess the diagnostic performance of diffusion-weighted MR imaging (DWI) in patients affected by prostatic fossa (PF) relapse after radical prostatectomy (RP) for prostatic carcinoma (PC). Methods. Twenty-seven patients showing a nodular lesion in the PF at T2-weighted MR imaging after RP, with diagnosis of PC relapse established by biopsy or PSA determinations, were investigated by DWI. Two readers evaluated the DWI results in consensus and the apparent diffusion coefficient (ADC) of the nodules, separately; a mean value was obtained (ADCm). Results. Relapses did not significantly differ in size in respect of postsurgical benign nodules. The DWI qualitative evaluation showed sensitivity, specificity, accuracy, ppv, and npv values, respectively, of 83.3%, 88.9%, 85.2%, 93.7%, and 72.7% (100%, 87.5%, 95.6%, 93.7%, and 100%, for nodules >6 mm). The intraclass correlation coefficient (ICC) for ADC evaluation between the two readers was 0.852 (95% CI 0.661–0.935; P = 0.0001). The ADCm values for relapses and benign nodules were, respectively, 0.98 ± 0.21 × 10−3 mm2/sec and 1.24 ± 0.32 × 10−3 mm2/sec (P = 0.006). Sensitivity, specificity, accuracy, ppv and npv of ADCm were, respectively, 77.8%, 88.9%, 81.8%, 93.3%, and 66.7% (93.3%, 87.5%, 85.4%, 93.3%, and 87.5% for nodules >6 mm). Conclusions. Diffusion-weighted MR imaging is a promising tool in the management of a hyperintense nodule detected by T2-weighted sequences. This might have a relevant importance in contouring radiotherapy treatment volumes.

3D bone texture analysis as a potential predictor of radiation-induced insufficiency fractures

Background The aim of our work is to assess the potential role of texture analysis (TA), applied to computed tomography (CT) simulation scans, in relation to the development of insufficiency fractures (IFs) in patients undergoing radiation therapy (RT) for pelvic malignancies. Methods We analyzed patients undergoing pelvic RT from Jan-2010 to Dec-2016, 31 of whom had developed IFs of the pelvis. We analyzed CT simulation scans using LifeX Software©, and in particular we selected three regions of interest (ROI): L5 body, the sacrum and both the femoral heads. The ROI were automatically contoured using the treatment planning software Raystation©. TA parameters included parameters from the gray-level histogram, indices from sphericity and from the matrix of GLCM (gray level co-occurrence matrix). The IFs patients were matched (1:1 ratio) with control patients who had not developed IFs, and were matched for age, sex, type of tumor, menopausal status, RT dose and use of chemotherapy. Univariate and multivariate analyses (logistic regression) were used for statistical analysis. Results Significant TA parameters on univariate analysis included both parameters from the histogram distribution, as well from the matrix of GLCM. On logistic regression analysis the significant parameters were L5-energy [P=0.033, odds ratio (OR): 1.997, 95% CI: 1.059-3.767] and FH-Skewness (P=0.014, OR: 2.338, 95% CI: 1.191-4.591), with a R2: 0.268. A ROC curve was generated from the binary logistic regression, and the AUC was 0.741 (95% CI: 0.627-0.855, P=0.001, S.E.: 0.058). Conclusions In our experience, 3D-bone CT TA can be used to stratify the risk of the patients to develop radiation-induced IFs. A prospective study will be conducted to validate these findings.

La volumetria con risonanza magnetica pesata in diffusione nella valutazione della risposta alla chemio-radioterapia nel tumore del retto: studio preliminare

PurposeThis study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (VDWI) and compared it with conventional T2-weighted volumetry (VC) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT).Materials and methodsFourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate VC. A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm2 and volume (VDWI) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen.ResultsInterobserver agreement was 0.977 [(95% confidence interval (CI) 0.954–0.989) and 0.956 (95% CI 0.905–0.980) for VC and VDWI and 0.964 (95% CI 0.896–0.988) and 0.271 (95% CI-0.267 to 0.686) between VC and VDWI before and after CHRT. The correlation between TRG and VC and VDWI was, respectively, rho = 0.597 (p<0.05) and r2=0.156 (p=0.162) and rho=0.847 (p<0.001).ConclusionsVDWI seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value.RiassuntoObiettivoScopo del nostro lavoro è stato valutare la fattibilità della volumetria in risonanza magnetica (RM) con immagini pesate in diffusione (VDWI) e confrontare tale metodo con la volumetria convenzionale (VC) basata su immagini T2-pesate in pazienti affetti da neoplasia rettale trattati con chemio-radioterapia (CHRT).Materiali e metodiQuattordici pazienti affetti da neoplasia rettale documentata istologicamente sono stati esaminati con RM prima e dopo chemio-radioterapia. Due osservatori hanno estrapolato indipendentemente il VC dalle immagini T2-pesate e il VDWI dall’acquisizione spin echo (SE)-echo-planar imaging (EPI)-diffusion-weighted (DW) (b-value 800 s/mm2) mediante segmentazione semiautomatica dell’iperintensità patologica. Le due volumetrie sono state comparate e correlate al grado di regressione tumorale sul pezzo operatorio (tumor regression grade, TRG).RisultatiL’accordo inter-osservatore per VC e VDWI è stato di 0,977 (95% intervallo di confidenza 0,954–0,989) e 0,956 (95% intervallo di confidenza 0,905–0,980) e tra VC e VDWI pre- e post-CHRT di 0,964 (95% intervallo di confidenza 0,896–0,988) e 0,271 (95% intervallo di confidenza −0,267–0,686). La correlazione tra TRG e VC e VDWI è stata rispettivamente di rho=0,597 (p<0,05) e rho=0,847 (p<0,001).ConclusioniLa VDWI sembra essere promettente per valutare la risposta alla CHRT nelle neoplasie rettali, tuttavia sono necessari ulteriori studi su casistiche più ampie al fine di migliorare la qualità di tale metodo e per valutarne il reale valore predittivo.

Assessment of response to chemoradiation therapy in rectal cancer using MR volumetry based on diffusion-weighted data sets: a preliminary report@@@La volumetria con risonanza magnetica pesata in diffusione nella valutazione della risposta alla chemio-radioterapia nel tumore del retto: studio preliminare

PurposeThis study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (VDWI) and compared it with conventional T2-weighted volumetry (VC) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT).Materials and methodsFourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate VC. A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm2 and volume (VDWI) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen.ResultsInterobserver agreement was 0.977 [(95% confidence interval (CI) 0.954–0.989) and 0.956 (95% CI 0.905–0.980) for VC and VDWI and 0.964 (95% CI 0.896–0.988) and 0.271 (95% CI-0.267 to 0.686) between VC and VDWI before and after CHRT. The correlation between TRG and VC and VDWI was, respectively, rho = 0.597 (p<0.05) and r2=0.156 (p=0.162) and rho=0.847 (p<0.001).ConclusionsVDWI seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value.RiassuntoObiettivoScopo del nostro lavoro è stato valutare la fattibilità della volumetria in risonanza magnetica (RM) con immagini pesate in diffusione (VDWI) e confrontare tale metodo con la volumetria convenzionale (VC) basata su immagini T2-pesate in pazienti affetti da neoplasia rettale trattati con chemio-radioterapia (CHRT).Materiali e metodiQuattordici pazienti affetti da neoplasia rettale documentata istologicamente sono stati esaminati con RM prima e dopo chemio-radioterapia. Due osservatori hanno estrapolato indipendentemente il VC dalle immagini T2-pesate e il VDWI dall’acquisizione spin echo (SE)-echo-planar imaging (EPI)-diffusion-weighted (DW) (b-value 800 s/mm2) mediante segmentazione semiautomatica dell’iperintensità patologica. Le due volumetrie sono state comparate e correlate al grado di regressione tumorale sul pezzo operatorio (tumor regression grade, TRG).RisultatiL’accordo inter-osservatore per VC e VDWI è stato di 0,977 (95% intervallo di confidenza 0,954–0,989) e 0,956 (95% intervallo di confidenza 0,905–0,980) e tra VC e VDWI pre- e post-CHRT di 0,964 (95% intervallo di confidenza 0,896–0,988) e 0,271 (95% intervallo di confidenza −0,267–0,686). La correlazione tra TRG e VC e VDWI è stata rispettivamente di rho=0,597 (p<0,05) e rho=0,847 (p<0,001).ConclusioniLa VDWI sembra essere promettente per valutare la risposta alla CHRT nelle neoplasie rettali, tuttavia sono necessari ulteriori studi su casistiche più ampie al fine di migliorare la qualità di tale metodo e per valutarne il reale valore predittivo.