18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment.

PURPOSE: [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis prediction in different tumors, but its role in esophageal cancer is still debated. The aim of this study was to evaluate the role of semiquantitative baseline PET parameters as possible prognostic and predictive factors in a series of esophageal carcinomas treated with combined modalities. METHODS: 43 patients with esophageal carcinoma were treated with chemoradiotherapy (CRT) followed by surgery in 20 cases and underwent pre-treatment 18F-FDG-PET/CT. Semiquantitative PET parameters were evaluated including Standardized Uptake Value (SUVmax e SUVmean), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) with isocontour of 41 and 50%. Further variables analyzed were gender, primary tumor site, histological type, use of surgery, achievement of a radical resection and the type of chemotherapy regimen. The correlation of all variables with treatment response, loco-regional control (LR), Overall survival (OS) and Disease-Free Survival (DFS) was evaluated. RESULTS: SUVmax, SUVmean50 and SUVmean41 were significantly higher in node-positive cases and in squamous cell carcinomas. With respect to prognostic factors, MTV was found to be correlated with OS: patients with MTV41 < 11.32 cm3 and MTV50 < 8.07 cm3 (both p values = 0.04) showed better 3-year OS rates (33 vs. 20%). Further factors predicting a better prognosis were the use of surgery and radical resection (R0) (both p values < 0.01). CONCLUSIONS: Pre-treatment MTV values were significant prognostic factors for OS, together with the use of surgery and R0 resection in esophageal cancers treated with multimodal therapies.

Does baseline [18F] FDG-PET/CT correlate with tumor staging, response after neoadjuvant chemoradiotherapy, and prognosis in patients with rectal cancer?

BACKGROUND: [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) may be used for tumor staging and prognosis in several tumors but its role in rectal cancer is still debated. The aim of the present study was to assess the correlation of baseline [18F] FDG-PET parameters with tumor staging, tumor response (tumor regression grade (TRG)), and outcome in a series of patients affected by locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT). METHODS: One hundred patients treated with neoadjuvant CRT and radical surgery were enrolled in the present study. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) at the baseline [18F] FDG-PET were calculated. These PET parameters were correlated with tumor staging, histopathological data (TRG1 vs. TRG2-5 and TRG1-2 vs. TRG3-5), disease-free survival, and overall survival. RESULTS: SUVmax and SUVmean of primary tumor were statistically associated with T4-stage. SUVmax, SUVmean, and TLG did not result statistically associated with TRG (TRG1 or TRG1-2). MTV resulted statistically associated with TRG1-2 group (OR 2.9; 95% CI 1.2-7.1). Finally, no PET parameter was significantly associated with disease-free or overall survival. CONCLUSION: Our results showed that baseline [18F] FDG-PET parameters correlated with tumor staging, and only MTV correlated with TRG 1-2. PET parameters failed to predict disease-free and overall survival after treatment completion. The results leave open to further studies the issue of identifying patients suitable for conservative approaches.

Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients.

BACKGROUND: To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. METHODS: A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7-12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. RESULTS: Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001), respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while 3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p < 0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001) were significantly correlated to pCR. The positive impact of interval (p < 0.001) was confirmed at multivariate analysis as the only correlated factor. CONCLUSION: We confirmed on a population-level that lengthening the interval (>13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

Anal cancer FDG-PET standard uptake value: correlation with tumor characteristics, treatment response and survival.

PURPOSE: The present work studies the correlation of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) standardized uptake value (SUV) with tumor characteristics, clinical response and prognosis in a series of anal canal cancer patients treated with chemo-radiotherapy. MATERIALS AND METHODS: Fifty-five patients were included in the present analysis. PET maximum SUV (SUVmax) of primary tumor was calculated for each patient. The correlation with clinical parameters, tumor response and survival data were analyzed. RESULTS: SUVmax significantly correlated with T-stage (p = 0.01) and histology (p = 0.03). Median SUVmax was higher for lesions with partial response (PR, 21/55, 38%) than for lesions with complete response (CR, 34/55, 62%) but without statistical significance (p = 0.17). The actuarial disease-free survival (DFS) and overall survival (OS) rates were 53.0 and 77.8% at 2 years and 41.3 and 58.6% at 5 years, respectively. Median SUVmax did not statistically correlate with clinical response or survival. CR and T1-T2 stage were statistically significant prognostic factors for disease-free survival (p < 0.0001 and p = 0.02, respectively) and CR was significant also for overall survival (p < 0.0001). CONCLUSIONS: Our data suggest that pre-treatment FDG-PET/CT SUVmax cannot directly predict tumor response and survival, but it is strongly associated with tumor characteristics such as primary tumor stage and histology, being the first one of the most important and validated prognostic factors for anal cancer.

Patterns of radiotherapy practice for pancreatic cancer: Results of the Gastrointestinal Radiation Oncology Study Group multi-institutional survey.

No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. In the present study, a nationwide survey using a questionnaire was performed to enquire the local standards for PC diagnosis and radiotherapy treatment. Fifty-seven percent of 140 Italian centres completed questionnaire. The main causes of no radiotherapy indication were poor general condition (45%) and lack of guidelines (25%). Physicians (38%) employed neoadjuvant therapy in locally advanced PC patients, while in other centres (62%) adjuvant chemoradiation was administered. Adjuvant gemcitabine-based chemotherapy was selected as the treatment of choice by 59% of centres. Patients were treated mostly with doses of 50-54.9 Gy on the tumour (or bed) plus lymph nodes. A 3D-CRT technique was used in 81.2% of centres, while IMRT and IGRT were available in 61.2 and 48.7% of cases, respectively. Extensive variation exists with regard to patterns of care for PC in Italy. Nevertheless, cooperative studies emerging from this survey appeared beneficial.

Patterns of practice in the radiation therapy management of rectal cancer: survey of the Interregional Group Piedmont, Valle d'Aosta and Liguria of the "Associazione Italiana di Radioterapia Oncologica (AIRO)".

AIMS AND BACKGROUND: To report the survey about the main aspects on the use of radiotherapy for the treatment of rectal cancer in Piedmont and Liguria. METHODS AND STUDY DESIGN: Sixteen centers (11 from Piedmont and 5 from Liguria) received and answered by email a questionnaire data base about clinical and technical aspects of the treatment of rectal cancer. All data were incorporated in a single data base and analyzed. RESULTS: Data regarding 593 patients who received radiotherapy for rectal cancer during the year 2009 were collected and analyzed. Staging consisted in colonoscopy, thoracic and abdominal CT, pelvic MRI and endoscopic ultrasound. PET/CT was employed to complete staging and in the treatment planning in 12/16 centers (75%). Neoadjuvant radiotherapy was employed more frequently than adjuvant radiotherapy (50% vs 36.4%), using typically a total dose of 45 Gy with 1.8 Gy/fraction. Concurrent chemoradiation with 5-fluorouracil or capecitabine was mainly employed in neoadjuvant and adjuvant settings, whereas oxaliplatin alone or in combination with 5-FU or capecitabine and leucovorin was commonly employed as the adjuvant agent. The median interval from neoadjuvant treatment to surgery was 7 weeks after long-course radiotherapy and 8 days after short-course radiotherapy. The pelvic total dose of 45 Gy in the adjuvant setting was the same in all the centers. Doses higher than 45 Gy were employed with a radical intent or in case of positive surgical margins. Hypofractionated regimens (2.5, 3 Gy to a total dose of 35-30 Gy) were used in the palliative setting. No relevant differences were observed in target volume definition and patient setup. Twenty-six patients (4.4%) developed grade 3 acute toxicity. Follow-up was scheduled in a similar way in all the centers. CONCLUSIONS: No relevant differences were found among the centers involved in the survey. The approach can help clinicians to address important clinical questions and to improve consistency and homogeneity of treatments.

Concomitant chemo-radiotherapy for unresectable oesophageal cancer: A mono-institutional study on 40 patients.

BACKGROUND/AIM: To analyse clinical response, overall (OS) and disease free survival (DFS) and toxicity in patients with unresectable oesophageal cancer treated by concomitant chemo-radiotherapy (CRT). MATERIALS AND METHODS: Forty patients with stage IIa-IVa biopsy proven oesophageal carcinoma were treated with CRT. All patients were studied with endoscopy and CT and judged unresectable after multidisciplinary discussion. CRT consisted of 3 cycles of cisplatin 100 mg/m(2) or carboplatin 300 mg/m(2) on day 1 and 5-fluorouracil 1000 mg/m(2) as a continuous infusion of 96 h associated with concurrent 3D-conformal RT. By using 15 MeV X-rays, a total dose of 60-66 Gy was delivered with daily fractions of 1.8-2.0 Gy. RESULTS: Complete response (CR), partial response (PR) and no response (NR) were observed in 50%, 20% and 20% of cases, respectively. Of the 20 patients with CR, 15 developed loco-regional recurrent disease. OS and DFS rates at 3 and 5 years were 38%, 8%, 49% and 10%, respectively. Total radiation dose ≥60 Gy improved loco-regional control and complete response (CR vs. PR + NR; p = 0.004) influenced both DFS and loco-regional control. Grade 3 gastrointestinal and haematological acute toxicity occurred in 3/40 patients (7.5%). One patient developed grade 4 renal failure. Late toxicity was reported in 2/40 patients (5.0%), consisting of grade 3 radiation pneumonitis. CONCLUSIONS: Concomitant CRT for unresectable oesophageal cancer can result in an acceptable loco-regional control with limited toxicity. Response after treatment and total radiation dose influenced the outcome.

Multidisciplinary approach in the treatment of malignant paraganglioma of the glomus vagale: a case report.

Malignant paraganglioma of the glomus vagale is a rare tumor entity originating from paraganglia or glomus cells. It typically affects middle age. It differs from benign paraganglioma because of its rapid growth and more aggressive clinical behavior. We report the case of a 40-year-old man presenting with a 5 cm lesion in the upper right cervical region detected by computed tomography (CT) and magnetic resonance imaging (MRI), which also showed enlargement of ipsilateral spinal and jugulodigastric lymph nodes with contrast enhancement. Clinical manifestations at diagnosis included a partial neurological deficit involving the right cranial nerves X, XI and XII. Tumor vascularization was assessed by digital angiography. The tumor mass was entirely removed by a right cervical approach with en-bloc resection with the regional lymph nodes. Histopathological examination showed a paraganglioma with cellular pleomorphism, necrotic microfoci, perineural infiltration and angiogenesis. Massive metastases in two of three jugulodigastric and one spinal lymph nodes on the right side were also detected. Postoperative workup included MRI, positron emission tomography (PET)/CT, meta-iodine-benzyl-guanidine (MIBG) scan, liver ultrasound and chest radiography. Subsequently, the patient underwent conformal radiotherapy with concomitant cisplatin administration. At the last clinical and radiological follow-up examination 5 years after completion of treatment, the patient was free of tumor recurrence. The integrated treatment by surgery and chemoradiation was feasible and effective in the management of this rare case of malignant paraganglioma of the glomus vagale. Multicenter studies should be done to increase the knowledge of tumor presentation and natural history and to analyze the possible treatment options.

Target volume delineation for preoperative radiotherapy of rectal cancer: inter-observer variability and potential impact of FDG-PET/CT imaging.

To analyze the inter-observer variability and the potential impact of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) imaging for target volume delineation in preoperative radiotherapy of rectal cancer. Gross tumor volume (GTV) and clinical target volume (CTV) in 2 cases of rectal cancer were contoured by 10 radiation oncologists, 5 on CT and 5 on PET/CT images. Resulting volumes were analyzed by coefficient of variation (CV) and concordance index (CI). Mean GTV was 120 cc +/- 20.4 cc in case A and 119 cc +/- 35.7 cc in case B. Mean CTV was 723 cc +/- 147.5 cc in case A and 739 cc +/- 195.6 cc in case B. CV was lower and CI was similar or higher across the observers contouring GTV on PET/CT. CTV variability was less influenced by the use of PET/CT. PET/CT may allow reducing inter-observer variability in GTV delineation.

FDG-PET/CT imaging for staging and target volume delineation in conformal radiotherapy of anal carcinoma.

BACKGROUND: FDG-PET/CT imaging has an emerging role in staging and treatment planning of various tumor locations and a number of literature studies show that also the carcinoma of the anal canal may benefit from this diagnostic approach. We analyzed the potential impact of FDG-PET/CT in stage definition and target volume delineation of patients affected by carcinoma of the anal canal and candidates for curative radiotherapy. METHODS: Twenty seven patients with biopsy proven anal carcinoma were enrolled. Pathology was squamous cell carcinoma in 20 cases, cloacogenic carcinoma in 3, adenocarcinoma in 2, and basal cell carcinoma in 2. Simulation was performed by PET/CT imaging with patient in treatment position. Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were drawn on CT and on PET/CT fused images. PET-GTV and PET-CTV were respectively compared to CT-GTV and CT-CTV by Wilcoxon rank test for paired data. RESULTS: PET/CT fused images led to change the stage in 5/27 cases (18.5%): 3 cases from N0 to N2 and 2 from M0 to M1 leading to change the treatment intent from curative to palliative in a case.Based on PET/CT imaging, GTV and CTV contours changed in 15/27 (55.6%) and in 10/27 cases (37.0%) respectively. PET-GTV and PET-CTV resulted significantly smaller than CT-GTV (p = 1.2 x 10(-4)) and CT-CTV (p = 2.9 x 10(-4)). PET/CT-GTV and PET/CT-CTV, that were used for clinical purposes, were significantly greater than CT-GTV (p = 6 x 10(-5)) and CT-CTV (p = 6 x 10(-5)). CONCLUSIONS: FDG-PET/CT has a potential relevant impact in staging and target volume delineation of the carcinoma of the anal canal. Clinical stage variation occurred in 18.5% of cases with change of treatment intent in 3.7%. The GTV and the CTV changed in shape and in size based on PET/CT imaging.

FDG-PET/CT imaging for staging and target volume delineation in preoperative conformal radiotherapy of rectal cancer.

PURPOSE: To investigate the potential impact of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on staging and target volume delineation for patients affected by rectal cancer and candidates for preoperative conformal radiotherapy. METHODS AND MATERIALS: Twenty-five patients diagnosed with rectal cancer T3-4 N0-1 M0-1 and candidates for preoperative radiotherapy underwent PET/CT simulation after injection of 5.18 MBq/kg of FDG. Clinical stage was reassessed on the basis of FDG-PET/CT findings. The gross tumor volume (GTV) and the clinical target volume (CTV) were delineated first on CT and then on PET/CT images. The PET/CT-GTV and PET/CT-CTV were analyzed and compared with CT-GTV and CT-CTV, respectively. RESULTS: In 4 of 25 cases (24%), PET/CT affected tumor staging or the treatment purpose. In 3 of 25 cases (12%) staged N0 M0, PET/CT showed FDG uptake in regional lymph nodes and in a case also in the liver. In a patient with a single liver metastasis PET/CT detected multiple lesions, changing the treatment intent from curative to palliative. The PET/CT-GTV and PET/CT-CTV were significantly greater than the CT-GTV (p = 0.00013) and CT-CTV (p = 0.00002), respectively. The mean difference between PET/CT-GTV and CT-GTV was 25.4% and between PET/CT-CTV and CT-CTV was 4.1%. CONCLUSIONS: Imaging with PET/CT for preoperative radiotherapy of rectal cancer may lead to a change in staging and target volume delineation. Stage variation was observed in 12% of cases and a change of treatment intent in 4%. The GTV and CTV changed significantly, with a mean increase in size of 25% and 4%, respectively.