FDG PET in response evaluation of bulky masses in paediatric Hodgkin's lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial.

PURPOSE: We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial. METHODS: We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors. RESULTS: Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01). CONCLUSION: After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.

Patterns of postoperative radiotherapy for head and neck cancer in Italy: a prospective, observational study by the head and neck group of the Italian Association for Radiation Oncology (AIRO).

AIMS AND BACKGROUND: Our previous survey showed that the patterns of postoperative radiotherapy (PORT) for head and neck cancer (HNC) in Italy might be suboptimal. A prospective observational study was therefore designed to evaluate this issue in greater detail. METHODS: All radiotherapy centers involved in the HNC Working Group of the Italian Radiation Oncology Association were asked to enter into the study all patients treated with PORT during a 6-month period. RESULTS: A total of 200 patients were accrued by 24 centers from December 2008 to May 2009. Larynx (38%) and oral cavity (34%) were the most common primary sites. The median time between surgery and the start of radiotherapy was 69 days (range, 25-215 days). Seventy-nine percent of cases with no evidence of risk factors for local recurrence were treated with high-dose radiotherapy to the primary site. In about 75% of cases the pN0 neck was included in the target volume. Concomitant chemotherapy was delivered to about 60% of patients with major risk factors and 21% of patients with no risk factors. CONCLUSIONS: Three issues emerged from our study as potential targets for future investigations: the impact on clinical outcome of the interval between surgery and the start of PORT; factors driving radiation oncologists to overtreat volumes at low risk of recurrence; and problems associated with the delivery of concomitant chemotherapy.

Evaluating the influence of the Siemens IGRT carbon fibre tabletop in head and neck IMRT.

BACKGROUND AND PURPOSE: To investigate the impact of a commercial IMRT/IGRT carbon-fibre tabletop in radiotherapy planning optimization and clinical dose distribution. MATERIALS AND METHODS: In this investigation the Siemens IGRT carbon fibre tabletop, routinely used for IMRT treatments in our Centre, has been incorporated into the CT volume of 6 IMRT patients. This was done by CT scanning the tabletop and by adding the obtained volume to the clinical dataset, acquired using the standard couch available in our CT scanner. This procedure was tested and validated for the purpose of this study. The radiotherapy plans have been optimized using both the original CT volume and the modified CT volume. RESULTS: IMRT optimization with the tabletop included in the clinical volume produced significantly different deliverable plans compared to standard optimized plans which did not include the treatment couch. Differences up to 6%/7% in terms of total number of MU were found in half of the clinical cases. Differences up to 37% in the number of MU per beam were also found. The number of iterations needed to reach an optimal solution also varied between -18% and +25%. Although the DVH analysis produced similar results, due to the fulfilment of the optimization objectives, differences higher than 10% were found in the dose calculated to superficial regions of the body. CONCLUSIONS: The results of this investigation show that the presence of the carbon fibre tabletop significantly affects the outcome of the beam parameters optimization. We suggest including carbon fibre tabletops into patient treatment planning dose calculation and optimization.

Feasibility single-arm study of a medical device containing Desmodium adscendens and Lithothamnium calcareum combined with chemotherapy in head and neck cancer patients.

BACKGROUND: Neoplasms of the head and neck represent approximately 5% of cancers and they require complex multidisciplinary clinical management. Desmodium adscendens (Desmodium) is a plant that possesses anti-allergic, antioxidant and hepatoprotective properties. Lithothamnium calcareum (Lithothamnium) is a calcified seaweed that possesses remineralization properties and the ability to maintain homeostasis. AIM: In this single-arm study, we investigated the efficacy of a combination therapy based on Desmovit® which contains Desmodium and Lithothamnium, and chemotherapy in patients with head and neck cancer. METHODS: Twelve patients with histological or cytological diagnosis of stage IV head and neck cancer were enrolled in this study that was approved by the ethics committee of the Unità Operativa Complessa (UOC) di Oncologia Medica Azienda Ospedaliera Ospedali Riuniti Marche Nord and followed the Declaration of Helsinki guidelines. The patients were monitored by investigation of the performance status according to the Glasgow Prognostic Score (GPS), which evaluates the plasma level of C-reactive protein and albumin levels, and the Eastern Cooperative Oncology Group (ECOG) examination. Pain and fatigue were also monitored using the visual analog scale and visual analog fatigue scale, respectively. All the above parameters were assessed biweekly to week 10. RESULTS: GPS, ECOG, and albumin remained stable throughout the study with a trend towards a decrease in GPS and albumin at week 10 post-treatment. Pain significantly improved at week 8 (P<0.05) while fatigue improved at weeks 8 and 10 (all P<0.01). CONCLUSION: We found that chemotherapy, combined with Desmodium and Lithothamnium, improved pain and fatigue in head and neck cancer patients, although we cannot confirm if this was due to Desmodium and Lithothamnium or chemotherapy. The improvement in pain and fatigue was supported by the ECOG performance status remaining stable with the highest score being equal to 2 throughout the study and a trend towards an improvement in GPS performance status and albumin levels.

Primary non-Hodgkin's lymphoma of the bone: treatment and analysis of prognostic factors for Stage I and Stage II.

PURPOSE: Primary non-Hodgkin's lymphomas of the bone (PLB) are very rare diseases accounting for 3%-5% of primary bone tumors. The best treatment for PLB has not been found yet. We report on the experience of the Radiation Oncology Department of Bologna University, Italy, relative to the diagnosis and treatment of this disease. METHODS AND MATERIAL: Seventy-seven patients with newly diagnosed PLB were treated from June 1983 to October 2001. Fifty-six were male (72.7%) and 21 were female (27.3%); the median age was 41.8 years, with a range of 16-84 years. The majority of patients had B-cell high-grade histology. The median follow-up was 149 months. Forty-four patients had a solitary bone lesion (Stage I); and in 33 patients, the tumor was spread to locoregional lymphatic area (Stage II). All patients were treated with radiotherapy (RT) with a median dose of 40 Gy (range, 36-54 Gy), and 67 received an additional anthracycline-based regimen of chemotherapy (combined modality therapy [CMT]). RESULTS: After therapy 73 of 77 patients (94.8%) reached a complete remission. At a median time of 23 months, 14 of 77 patients (18.2%) had a disease relapse. Four of them were treated with RT alone (in these cases tumor lesions were <3 cm and located at sites different from mandible); 10 patients were treated with combined RT and CMT. Actuarial disease-free survival (DFS) and overall survival (OS) at 15 years were, respectively, 76.6% and 88.3%. No local failures were seen. Prognostic factors such as age, sex, stage, and bulky lesions were analyzed. Age (<40 vs. >40 years) was the only significant factor for DFS (85.3% vs. 66.6%, p = 0.03). Bulky lesions apparently did not affect OS (90.9% vs. 72.7%). However, the difference has no statistical significance (p = 0.05). Acute and late toxicity related to the treatment was moderate. CONCLUSIONS: In PLB the CMT seems to produce a better outcome than RT alone; that still remains the best treatment for local disease control. Radiation therapy alone should be reserved for mandibular tumors, which are usually very small and earlier diagnosed.

[Intracoronary beta-radiotherapy in high-risk in-stent restenosis. Prospective results of a single center registry]. / Efficacia a lungo termine della brachiterapia endocoronarica beta (32P) nel trattamento delle ristenosi intrastent ad elevato rischio. Risultati prospettici di un registro monocentrico.

BACKGROUND: The aim of the study was to evaluate, on single center prospective data, long-term angiographic and clinical results of intracoronary beta (32P) brachytherapy in "real world" patients with high-risk in-stent restenosis lesions. METHODS: Sixty-nine consecutive patients (77 lesions) with high-risk in-stent restenosis (mean lesion length 30.3 +/- 16.1 mm, pattern III-IV 57.2%, diabetes 33.3%) treated with percutaneous dilation procedures and beta-radiation therapy, underwent 7-month clinical and angiographic follow-up. RESULTS: One patient (1.4%) presented with procedural non-Q wave myocardial infarction. At a mean follow-up of 7 +/- 1.5 months, death was observed in 1 patient (1.4%) and non-Q wave myocardial infarction in 3 (4.3%) (in 2 patients, who prematurely discontinued antiplatelet therapy, caused by late coronary thrombosis). Seven-month binary angiographic restenosis occurred in 20 lesions (25.9%) (in-stent restenosis 11.6%). Target lesion and target vessel revascularization occurred in 20 (28.9%) and 21 (30.4%) patients. At follow-up only 12 (17.3%) patients presented with CCS class III-IV angina. After intracoronary beta brachytherapy angiographic restenosis occurred regardless of the vessel size, lesion length and ostial location. On the contrary a high restenosis rate was documented in obstructive lesions. CONCLUSIONS: As applied in routine clinical practice, radiation therapy is safe and effective in the treatment of high-risk in-stent restenosis. In spite of all that, total occlusion at baseline predicts late angiographic restenosis.

Usefulness of 64Cu-ATSM in head and neck cancer: a preliminary prospective study.

AIMS: Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) is a hypoxia-avid, positron emitter radiotracer. The primary aim of this study is to assess the efficacy of pretherapy Cu-ATSM PET/CT as a prognostic factor of response to therapy. The secondary aims are to investigate if there is a difference between early and late PET/CT scans and if there is a difference between the biologic tumor volume (BTV) in radiotherapy treatment planning calculated between Cu-ATSM and F-FDG, and to assess if Cu-ATSM is a prognostic marker of disease progression. METHODS: Eleven patients with head and neck cancer treated with chemoradiotherapy were enrolled prospectively; both Cu-ATSM and F-FDG PET/CT scans before and after treatment were obtained. The Cu-ATSM scans were performed after 1 hour (early) and 16 hours (late). RESULTS: All patients had stage III or IV squamous cell head and neck cancer; 7 of 11 patients had nodal metastasis, and 22 cancer foci were detected with Cu-ATSM. SUVmax was 16.2 ± 7.9, and there was no significant SUVmax difference between early and late imaging. F-FDG SUVmax before therapy was 15.6 ± 9.4, whereas F-FDG SUVmax after therapy was 1.5 ± 1.2. Sensitivity and specificity values of Cu-ATSM calculated with receiver operating characteristic curves were 100% and 50% considering the SUVmax and 100% and 33% considering the volume, respectively. No difference has been found between the BTV contoured with Cu-ATSM and F-FDG. CONCLUSIONS: The Cu-ATSM scans showed high sensitivity but low specificity in predicting neoadjuvant chemoradiotherapy response. No difference was noted between early and late scans. F-FDG and Cu-ATSM provided similar results about delineation of BTV.

Changes in patterns of practice for prostate cancer radiotherapy in Italy 1995-2003. A survey of the Prostate Cancer Study Group of the Italian Radiation Oncology Society.

AIMS AND BACKGROUND: In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one. METHODS: Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey. RESULTS: Significant differences in clinical management (-10% had abdominal magnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001). CONCLUSIONS: The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Combined 18F-FDG-PET/CT imaging in radiotherapy target delineation for head-and-neck cancer.

PURPOSE: To evaluate the effect of the use of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in radiotherapy target delineation for head-and-neck cancer compared with CT alone. METHODS AND MATERIALS: A total of 38 consecutive patients with head-and-neck cancer were included in this study. The primary tumor sites were as follow: 20 oropharyngeal tumors, 4 laryngeal tumors, 2 hypopharyngeal tumors, 2 paranasal sinuses tumors, 9 nasopharyngeal tumors, and 1 parotid gland tumor. The FDG-PET and CT scans were performed with a dedicated PET/CT scanner in one session and then fused. Subsequently, patients underwent treatment planning CT with intravenous contrast enhancement. The radiation oncologist defined all gross tumor volumes (GTVs) using both the PET/CT and CT scans. RESULTS: In 35 (92%) of 38 cases, the CT-based GTVs were larger than the PET/CT-based GTVs. The average total GTV from the CT and PET/CT scans was 34.54 cm(3) (range, 3.56-109) and 29.38 cm(3) (range, 2.87-95.02), respectively (p < 0.05). Separate analyses of the difference between the CT- and PET/CT-based GTVs of the primary tumor compared with the GTVs of nodal disease were not statistically significant. The comparison between the PET/CT-based and CT-based boost planning target volumes did not show a statistically significant difference. All patients were alive at the end of the follow-up period (range, 3-38 months). CONCLUSION: GTVs, but not planning target volumes, were significantly changed by the implementation of combined PET/CT. Large multicenter studies are needed to ascertain whether combined PET/CT in target delineation can influence the main clinical outcomes.

Long-term clinical and angiographic outcome of patients with occlusive in-stent restenosis treated with (32P) beta-brachytherapy.

The objective of this study was to determine the safety and efficacy of (32)P beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). (32)P beta-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR.

Predictors of 32P beta brachytherapy failure in patients with high-risk in-stent restenosis.

BACKGROUND: The effectiveness of coronary radiation therapy for the treatment of in-stent restenosis (ISR) has been established in several randomized clinical trials. The efficacy of this treatment in the general population is less well established. METHODS AND MATERIALS: We report our experience in 118 consecutive patients with nonselected high-risk ISR who had undergone successful percutaneous coronary intervention and brachytherapy with (32)P beta-irradiation and who were prospectively enrolled in a quantitative angiographic and clinical follow-up protocol at 7 months after the index procedure. The aim of this study was to investigate the independent predictor of angiographic restenosis after (32)P brachytherapy treatment. RESULTS: Of the patients, 28.8% were diabetics. The mean lesion and mean radiated lengths were, respectively, 30.1 +/- 17.2 and 43.8 +/- 16.9 mm. The ISR pattern was diffuse in 96% of the treated lesions; in particular, 22.1% presented an occlusive pattern and 37.1% a proliferative pattern. At follow-up angiographic, restenosis and major adverse cardiac events (MACE) rates were, respectively, 20.8% and 29.6%. The univariate predictors of angiographic restenosis were procedural geographic miss, pattern IV ISR, manual pullback maneuver of the radiation source, preprocedural lesion percentage stenosis and preprocedural lesion MLD. At logistic regression analysis, only geographic miss and pattern IV ISR were independent predictors of post intracoronary radiation therapy (IRT) angiographic restenosis. CONCLUSION: These data indicate that 7-month angiographic restenosis after (32)P IRT in complex patients with ISR is not a frequent event and is predicted mainly by an occlusive lesion at baseline and by procedural geographical miss.