Decommissioning procedure and induced activation levels, calculations and measurements in an 18 MeV medical cyclotron.

The present article describes the decommissioning of a self-shielded 18 MeV medical cyclotron IBA Cyclone 18/9 after 14 years of operation. A Monte Carlo simulation of the possible nuclear reactions was performed in order to plan the decommissioning activities. During the cyclotron dismantling, the activities of the cyclotron components, concrete wall and floor samples were measured. Residual activities were analysed by means of an HPGe detector and liquid scintillation counting, and compared with simulation data. Dosimetry of the staff involved in the decommissioning procedure was monitored by individual TL dosimeters and/or digital dosimeter. The cyclotron component analysis confirmed the presence of gamma and pure beta emitters,22Na,54Mn,60Co,65Zn,207Bi,55Fe,63Ni at different values of specific activity, depending on the positioning of the sample point and on the alloy of the sampled part. In these components the presence of gamma and pure beta emitters was measured 5 years after the shutdown at levels far above clearance limits as defined by the 'Recommended radiological protection criteria for the recycling of metals from the dismantling of nuclear installations' (RP89) guidelines. The simulation, carried out by FLUKA Code (version 2020.0.5) on the cyclotron components, provided good agreement with measurements, with a maximum discrepancy of the same order as the uncertainties. Four engineers of the cyclotron maintenance staff were involved in the dismounting of the hottest components and rigging of the cyclotron in the deposit 6 months after shutdown and two engineers were involved during the drilling phase 3.5 years after shutdown. The measured dose from external exposure of the involved staff was lower than 100µSv person-1during the first phase and lower than 20µSv person-1during the final drilling phase. Measured doses from intake were negligible. In conclusion, the decommissioning of the 18 MeV cyclotron does not represent a risk for the involved staff, but, due to the presence of long-lived radioisotopes, the cyclotron components are to be treated as low level radioactive waste, and stored in an authorised storage area for at least 25 years after shutdown.

Monitoring skin dose changes during image-guided helical tomotherapy for head and neck cancer patients.

PURPOSE: An increase of skin dose during head and neck cancer (HNC) radiotherapy is potentially dangerous. Aim of this study was to quantify skin dose variation and to assess the need of planning adaptation (ART) to counteract it. METHODS: Planning CTs of 32 patients treated with helical tomotherapy (HT) according to a Simultaneous Integrated Boost (SIB) technique delivering 54/66 Gy in 30 fractions were deformably co-registered to MVCTs taken at fractions 15 and 30; in addition, the first fraction was also considered. The delivered dose-of-the-day was calculated on the corresponding deformed images. Superficial body layers (SL) were considered as a surrogate for skin, considering a layer thickness of 2 mm. Variations of SL DVH (∆SL) during therapy were quantified, focusing on ∆SL95% (i.e., 62.7 Gy). RESULTS: Small changes (within ± 1 cc for ∆SL95%) were seen in 15/32 patients. Only 2 patients experienced ∆SL95% > 1 cc in at least one of the two monitored fractions. Negative ∆SL95% > 1 cc (up to 17 cc) were much more common (15/32 patients). The trend of skin dose changes was mostly detected at the first fraction. Negative changes were correlated with the presence of any overlap between PTV and SL at planning and were explained in terms of how the planning system optimizes the PTV dose coverage near the skin. Acute toxicity was associated with planning DVH and this association was not improved if considering DVHs referring to fractions 15/30. CONCLUSION: About half of the patients treated with SIB with HT for HNC experienced a skin-sparing effect during therapy; only 6% experienced an increase. Our findings do not support skin-sparing ART, while suggesting the introduction of improved skin-sparing planning techniques.

Organ doses and lifetime attributable risk evaluations for scoliosis examinations of adolescent patients with the EOS imaging system.

PURPOSE: The goal of this work is to evaluate organ doses and lifetime attributable risk of cancer incidence and mortality in scoliosis examinations of adolescent patients performed with EOS imaging system, in order to optimize patient dose and protocols. METHODS: An anthropomorphic phantom of a normal patient, with thermoluminescent dosimeters in correspondence with the main organs at risk, was imaged with both EOS and computed radiography (CR). For each modality, effective dose was calculated from the measured organ doses. Lifetime attributable risk was computed accordingly to the Committee on the Biological Effects of Ionizing Radiation (BEIR VII) and Public Health England (HPA) publications. RESULTS: Except for testes and eyes, which were excluded from the scan in CR protocol, for all the other organs the doses delivered with CR examination were higher than these delivered by EOS system. The effective dose in EOS examination (0.43 ± 0.04 mSv) is about two times less than the dose in computed radiography with anti-scatter grid examination (0.87 ± 0.09 mSv), and, consequently, also the cancer probability is lower (5.4 vs 9.7 number of any cancers induction cases per 100,000 person examined, for a 20-year-old male patient). CONCLUSIONS: The EOS system is efficient in limiting patient dose. The shielding of testes and the exclusion of eyes from the scan could allow to further reduce the dose.

Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

OBJECTIVE: To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. PATIENTS AND METHODS: From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). RESULTS: With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. CONCLUSIONS: 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients.

Early volume variation of positive lymph nodes assessed by in-room mega voltage CT images predicts risk of loco-regional relapses in head and neck cancer patients treated with intensity-modulated radiotherapy.

BACKGROUND: We investigated the possibility to early identify non-responding patients based on FDG-PET positive lymph nodes (PNs) volume variation assessed with in-room images. MATERIAL AND METHODS: Twenty-seven head and neck cancer patients with at least one pre-treatment PNs were retrospectively analyzed; they received 54 Gy, 66 Gy, 69 Gy in 30 fractions on precautionary lymph nodal (N), primary (T) and PET positive (BTV) planning target volumes (PTVs), respectively with Helical TomoTherapy (SIB approach). PNs volume changes during treatment were assessed based on megavoltage computed tomography (MVCT) used for image guidance as ratio between volumes at fractions 10/20/30 and at first fraction. Data on T, N and M relapses (rT, rN, rM) were collected for all patients. The difference of PNs volume changes, during treatment, between patients with versus without relapses was tested (Mann-Whitney test). The impact of shrinkage on the corresponding survival curves (Cox proportional-hazard regression), dividing between no/moderate versus large shrinkage (based on ROC curve best cut-off value) was also investigated. RESULTS: Median follow-up was 27.4 m (3.7-108.9). The numbers for rT, rN, rM were 5, 4, 6, respectively. Differences in PNs shrinkage were found between patients with and without rT/rN at all considered timing [fr 20, rT: 0.56 vs. 1.07 (median), p = 0.06; rN: 0.57 vs. 1.25, p = 0.07]. Differences were lower for rM. Survival curves provide high hazard ratios (HR) between PNs changes and rT/rN at all considered timing [fr 20, rT: best cut-off = 0.58, HR 5.1 (95% CI 0.5-49.4), p = 0.12; rN: best cut-off = 0.98, HR 14.9 (1.6-142.9), p = 0.01]. CONCLUSION: A limited shrinkage of PNs during treatment is associated with poorer outcome in terms of T/N relapses. The early variation of PNs observed on in-room images may provide useful information about the individual response with potential application in guiding an early adaptation of the treatment.

Multidetector computed tomography for coronary stents imaging: high-voltage (140-kVp) prospective ECG-triggered versus standard-voltage (120-kVp) retrospective ECG-gated helical scanning.

OBJECTIVE: To compare prospective electrocardiogram (ECG)-triggered high-voltage coronary computed tomography (CT) angiography (CTA; 140-kVp P-cCTA) with retrospective ECG-gated standard-voltage cCTA (120-kVp R-cCTA), in patients with coronary stents. METHODS: Fifty-two patients with coronary stents were studied with 64-slice multidetector scanner. Ninety-three stents were analyzed: 55 with 140-kVp P-cCTA and 38 with 120-kVp R-cCTA. Image quality (IQ), diagnostic confidence (DC), in-stent assessable lumen, artificial narrowing, and effective radiation dose were compared between techniques. RESULTS: Image quality and DC were significantly better for the 140-kVp P-cCTA in comparison with the 120-kVp R-cCTA (IQ, 1.1 ± 0.36 vs 1.7 ± 0.60, respectively; P < 0.00001. Diagnostic confidence: 1.1 ± 0.29 vs 1.5 ± 0.65 respectively; P < 0.0001). In-stent assessable lumen and artificial narrowing were comparable between the techniques. Effective dose was lower for the 140-kVp P-cCTA (6.7 ± 2.07 mSv vs 15.8 ± 6.89 mSv; P < 0.0001). CONCLUSIONS: High voltage combined with axial prospective ECG-triggered scan improved IQ and DC in stent cCTA imaging but failed to improve the diameter of in-stent assessable lumen and to reduce the artificial narrowing compared with the 120-kVp R-cCTA. Effective dose was 60% lower for the 140-kVp P-cCTA.

Characterisation of rectal motion during neo-adjuvant radiochemotherapy for rectal cancer with image-guided tomotherapy: implications for adaptive dose escalation strategies.

BACKGROUND: Interest in boosting the dose to the tumour during neo-adjuvant radiochemotherapy for rectal cancer is ever increasing, especially within the frame of adaptive radiotherapy. Rectal motion remains a potentially important obstacle to the full exploitation of this approach and needs to be carefully investigated. MATERIAL AND METHODS: The main purposes of this work were to: a) quantify rectal motion on all fractions of a treatment course; and b) assess margins for adaptive boosting in the second part of the treatment in order to benefit of tumour reduction during treatment. Ten consecutive patients treated with image-guided tomotherapy (41.4 Gy, 18 fractions) were selected. The cranial half of the rectum (subject to motion) was contoured by a single observer on daily MVCTs. The variations of rectal volume and of the envelope of rectum positions were investigated (169 MVCTs). The impact of applying different margins to the rectum in including all its possible positions was also investigated when considering the planning kVCT, the first fraction MVCT, the half-treatment MVCT or the median rectal contours of the whole or second half of treatment as reference volumes. RESULTS: Rectal volume reduced during treatment in all patients, with a significant time-trend in 6/10 patients. The median values of the envelope volumes were 129 cm(3) and 87 cm(3) in the first and second half of the treatment, respectively. On average, 95% of the rectal envelope was included by an isotropic expansion of 12 mm and 5 mm of the median contours when considering the whole or the second half of the treatment, respectively. CONCLUSION: A significant reduction of rectal volume was found in the second part of the treatment where rectal mobility was limited. As a consequence, relatively small margins may be used around the residual tumour volume when adaptive boost is delivered in the second half of the treatment.

Multispectral Cerenkov luminescence tomography for small animal optical imaging.

Quite recently Cerenkov luminescence imaging (CLI) has been introduced as a novel pre-clinical imaging for the in vivo imaging of small animals such as mice. The CLI method is based on the detection of Cerenkov radiation (CR) generated by beta particles as they travel into the animal tissues with an energy such that Cerenkov emission condition is satisfied. This paper describes an image reconstruction method called multi spectral diffuse Cerenkov luminescence tomography (msCLT) in order to obtain 3D images from the detection of CR. The multispectral approach is based on a set of 2D planar images acquired using a number of narrow bandpass filters, and the distinctive information content at each wavelength is used in the 3D image reconstruction process. The proposed msCLT method was tested both in vitro and in vivo using 32P-ATP and all the images were acquired by using the IVIS 200 small animal optical imager (Caliper Life Sciences, Alameda USA). Source depth estimation and spatial resolution measurements were performed using a small capillary source placed between several slices of chicken breast. The theoretical Cerenkov emission spectrum and optical properties of chicken breast were used in the modelling of photon propagation. In vivo imaging was performed by injecting control nude mice with 10 MBq of 32P-ATP and the 3D tracer bio-distribution was reconstructed. Whole body MRI was acquired to provide an anatomical localization of the Cerenkov emission. The spatial resolution obtained from the msCLT reconstructed images of the capillary source showed that the FWHM is about 1.5 mm for a 6 mm depth. Co-registered MRI images showed that the Cerenkov emission regions matches fairly well with anatomical regions, such as the brain, heart and abdomen. Ex vivo imaging of the different organs such as intestine, brain, heart and ribs further confirms these findings. We conclude that in vivo 3D bio-distribution of a pure beta-minus emitting radiopharmaceutical such as 32P-ATP can be obtained using the msCLT reconstruction approach.

PET-guided dose escalation tomotherapy in malignant pleural mesothelioma.

PURPOSE: To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). RESULTS: Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p=0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p=0.003). CONCLUSIONS: The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.

In vivo ¹8F-FDG tumour uptake measurements in small animals using Cerenkov radiation.

PURPOSE: 2-[(18)F]Fluoro-2-deoxy-D-glucose ((18)F-FDG) is a widely used PET radiotracer for the in vivo diagnosis of several diseases such as tumours. The positrons emitted by (18)F-FDG, travelling into tissues faster than the speed of light in the same medium, are responsible for Cerenkov radiation (CR) emission which is prevalently in the visible range. The purpose of this study is to show that CR escaping from tumour tissues of small living animals injected with (18)F-FDG can be detected with optical imaging (OI) techniques using a commercial optical instrument equipped with charge-coupled detectors (CCD). METHODS: The theory behind the Cerenkov light emission and the source depth measurements using CR is first presented. Mice injected with (18)F-FDG or saline solution underwent dynamic OI acquisition and a comparison between images was performed. Multispectral analysis of the radiation was used to estimate the depth of the source of Cerenkov light. Small animal PET images were also acquired in order to compare the (18)F-FDG bio-distribution measured using OI and PET scanner. RESULTS: Cerenkov in vivo whole-body images of tumour-bearing mice and the measurements of the emission spectrum (560-660 nm range) are presented. Brain, kidneys and tumour were identified as a source of visible light in the animal body: the tissue time-activity curves reflected the physiological accumulation of (18)F-FDG in these organs. The identification is confirmed by the comparison between CR and (18)F-FDG images. CONCLUSION: These results will allow the use of conventional OI devices for the in vivo study of glucose metabolism in cancer and the assessment, for example, of anti-cancer drugs. Moreover, this demonstrates that (18)F-FDG can be employed as it is a bimodal tracer for PET and OI techniques.

Planning design of locally advanced pancreatic carcinoma using 4DCT and IMRT/IGRT technologies.

BACKGROUND AND PURPOSE: to study the impact of the 4DCT imaging technique on radiotherapy planning for pancreatic carcinoma. To evaluate the possibility of IMRT/IGRT to increase the dose to PTV subvolume. MATERIAL AND METHODS: contrast-enhanced 4DCT scans of 15 patients (PTs) with unresectable pancreatic cancer were acquired. A 4DCT based PTV (4D-PTV) was created by the convolution of contours and then expanded for geometric uncertainties; a standard PTV (STD-PTV) was derived from a single CTV plus conventional margins. Two 3D conformal treatment (3DCRT) plans and one Helical Tomotherapy (HT) plan were generated with a prescription of 60 Gy. Regarding the 3DCRT plans, the 4D-PTV was considered as the target volume for one, and the STD-PTV for the other; the HT plans were performed only for 4D-PTV. Twelve of 15 PTs were admitted to a Phase I hypofractionated study (15 fractions). The prescribed dose was 44.25 Gy to the 4D-PTV and the PTV subvolume around vascular involvement was boosted from 50 to 55 Gy; before treatment, daily patient position was corrected using MVCT. RESULTS: 4D-PTVs were smaller than STD-PTVs with a volume reduction equal to 37%. 3DCRT plans on 4D-PTV showed a significant sparing of most OARs, the use of IMRT allowed a further significant dose reduction. In the Phase I study the PTV subvolume received up to 55 Gy with modest increase in dose to OARs. CONCLUSIONS: the 4DCT procedure decreases the overlap between PTV and OARs. HT technique, compared with 3DCRT, allows efficient dose sparing in particular for the duodenum. The IMRT/IGRT approach allows a safe dose escalation to PTV subvolume.

Feasibility of safe ultra-high (EQD(2)>100 Gy) dose escalation on dominant intra-prostatic lesions (DILs) by Helical Tomotheraphy.

PURPOSE: to verify the possibility of using Helical Tomotherapy to safely escalate dose to single or multiple highly radioresistant dominant intra-prostatic lesions (DILs) as assessed by functional magnetic resonance imaging (MRI). MATERIAL: in seven intermediate/high risk patients, T2WI, T1WI and DWI MRI imaging showed evidence of one DIL in four patients and two DILs in three patients in the peripheral zone of the prostate. The planning strategy was to deliver median doses of 80, 90, 100 and 120 Gy to PTVDIL while delivering 71.4 Gy/28 fractions (EQD(2)=75 Gy) to the remaining portion of PTV. A higher priority was assigned to rectal constraints relative to DIL coverage. Rectal NTCP calculations were performed using the most recently available model data. RESULTS: the median dose to DIL could safely be escalated to at least 100 Gy (EQD(2,α/ß=10)=113 Gy) without violating safe constraints for the organs at risk. Typical rectal NTCP values were around or below 1-3% for G3 toxicity and 5-7% for G2-G3 toxicity. For the 100 Gy DIL dose boost strategy, mean D95% of DIL and PTVDIL were 98.8 Gy and 86.7 Gy, respectively. The constraints for bladder, urethra and femoral heads were always respected. CONCLUSIONS: IGRT by Helical Tomotherapy may permit the safe escalation of EQD(2,α/ß=10) to at least 113 Gy to DILs without significantly increasing rectal NTCP compared to plans without dose escalation. A Phase I-II clinical study is warranted.

Megavoltage CT images of helical tomotherapy unit for radiation treatment simulation: impact on feasibility of treatment planning in a prostate cancer patient with bilateral femoral prostheses.

Metal prosthesis artefacts on CT images can be a significant problem in the definition of volumes of interest, dose calculation and patient setup in modern radiotherapy. We experienced considerable difficulties in defining the organs at risk and treatment volumes on kVCT images of standard CT simulation in a prostate cancer patient due to the presence of bilateral femoral prostheses causing artefacts. As shown in the current case, MVCT images of the patient in the treatment position obtained using a helical tomotherapy unit can provide sufficient morphological information to define the pelvic anatomic structures for radical prostate treatment planning. The patient completed the planned treatment and at 90 days after the end of treatment no severe side effects were recorded. Since there have been few reports on the use of MVCT images to overcome the problem of hip prosthesis artefacts, a brief literature review was also carried out.

Knowledge-based automatic optimization of adaptive early-regression-guided VMAT for rectal cancer.

PURPOSE: To implement a knowledge-based (KB) optimization strategy to our adaptive (ART) early-regression guided boosting technique in neo-adjuvant radio-chemotherapy for rectal cancer. MATERIAL AND METHODS: The protocol consists of a first phase delivering 27.6 Gy to tumor/lymph-nodes (2.3 Gy/fr-PTV1), followed by the ART phase concomitantly delivering 18.6 Gy (3.1 Gy/fr) and 13.8 Gy (2.3 Gy/fr) to the residual tumor (PTVART) and to PTV1 respectively. PTVART is obtained by expanding the residual GTV, as visible on MRI at fraction 9. Forty plans were used to generate a KB-model for the first phase using the RapidPlan tool. Instead of building a new model, a robust strategy scaling the KB-model to the ART phase was applied. Both internal and external validation were performed for both phases: all automatic plans (RP) were compared in terms of OARs/PTVs parameters against the original plans (RA). RESULTS: The resulting automatic plans were generally better than or equivalent to clinical plans. Of note, V30Gy and V40Gy were significantly improved in RP plans for bladder and bowel; gEUD analysis showed improvement for KB-modality for all OARs, up to 3 Gy for the bowel. CONCLUSIONS: The KB-model generated for the first phase was robust and it was also efficiently adapted to the ART phase. The performance of automatically generated plans were slightly better than the corresponding manual plans for both phases.

Prostate cancer with low burden skeletal disease at diagnosis: outcome of concomitant radiotherapy on primary tumor and metastases.

OBJECTIVE: To evaluate toxicity and clinical outcome in synchronous bone only oligometastatic (≤2 lesions) prostate cancer patients, simultaneously irradiated to prostate/prostatic bed, lymph nodes and bone metastases. METHODS: From 2/2009 to 6/2015, 39 bone only prostate cancer patients underwent radiotherapy (RT) at "radical" doses to bone metastases (median 2 Gy equivalent dose, EQD2>40Gy, α/ß = 1,5), nodes, and prostate/prostatic bed, within the same RT course, in association with androgen deprivation therapy (ADT).Biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were evaluated. RESULTS: After a median follow-up of 46.5 (1.2-103.6) months, 5 patients died from disease progression, 10 experienced biochemical relapse, 19, still in ADT, presented undetectable prostate-specific antigen (PSA) at the last follow-up. Five patients who discontinued ADT after a median of 34 months (5.8-41) are free from biochemical relapse.The 4 year Kaplan-Meier estimates of biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were 53.3%, 65.7%, 73.4% and 82.4% respectively.No Grade > 2 acute events and only two severe late urinary events were recorded, not due to the concomitant treatment of primary and metastatic disease. CONCLUSION: Our results suggest that "radical" and synchronous irradiation of primitive tumor and metastatic disease may be a valid approach in synchronous bone only prostate cancer patients, showing mild toxicity profile and promising survival results. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first analysis of clinical outcome in synchronous bone-only metastasis (neither nodal nor visceral) patients at diagnosis, treated with radical RT to all disease, associated to ADT.

Helical tomotherapy for scalp recurrence of primary eccrine mucinous adenocarcinoma.

Primary cutaneous mucinous carcinomas originating from sweat glands are rare tumors with patterns of spread that are difficult to predict. We present a case of a five times recurring eccrine mucinous adenocarcinoma of the scalp, previously treated with surgery and adjuvant radiation therapy. After magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (18FDG-PET/CT), which documented local recurrence, the patient was considered eligible for salvage irradiation of the scalp. We decided to use helical tomotherapy, which combines conformity of dose delivery with the possibility of daily control of the setup accuracy. Forty gray (2Gy/fraction) to the planning target volume and 50 Gy (2.5Gy/fraction) to the biological target volume defined on the basis of 18FDG-PET/CT was prescribed with a simultaneous integrated boost technique. After 12 fractions the patient was submitted to intermediate evaluation by 18FDG-PET/CT, which showed a partial response to the treatment. After 2, 4, 8, and 12 months, 18FDG-PET/CT showed a complete metabolic local response. This experience suggests a possible role of 18FDG-PET/CT-guided helical tomotherapy as an alternative to repeated and frequently demolitive surgery approaches.

Clinical implementation of low-dose total body irradiation using topotherapy technique.

BACKGROUND AND PURPOSE: The topotherapy technique was recently suggested as a robust alternative to helical radiation delivery for total body irradiation (TBI). It allows to deliver a discrete number of beams with fixed gantry. A Topotherapy-based low-dose TBI technique was optimized and clinically implemented. MATERIALS AND METHODS: TBI delivery was split in two parts: the first treating from the head to half thigh and the second the remaining legs. An in-silico investigation aimed to optimize plan parameters was first carried out on four patients. For the upper plan, field width and pitch were fixed to 5 cm and 0.5: the combined impact of five modulation factor (MF) values and different field configurations (6/8/12 fields) was investigated. For the lower plan, two anterior/posterior beams (field width: 5 cm; pitch: 0.5; MF:1.5) were used. After assessing the optimal technique, set-up/quality assurance/image-guidance procedures were defined and the technique clinically implemented: 23 patients were treated up to now. RESULTS: The best compromise between treatment time and planning target volume (PTV) coverage/homogeneity was found for MF = 1.5 and 8 fields. All clinical plans were automatically optimized using an "ad-hoc" plan template: excellent PTV coverage (PTV95%>98.5%) and homogeneity (median SD:4%) were found with a median beam-on time of 17/9 min for the upper/lower plan. All patients were successfully treated and transplanted. CONCLUSIONS: TBI delivered with the topotherapy approach robustly guarantees adequate coverage and dose homogeneity. Semi-automatic clinical plans can be quickly generated and efficiently delivered.

Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs.

INTRODUCTION: The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. METHODS AND MATERIALS: From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients. RESULTS: The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001). CONCLUSIONS: Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.

Early variation of 18-fluorine-labelled fluorodeoxyglucose PET-derived parameters after chemoradiotherapy as predictors of survival in locally advanced pancreatic carcinoma patients.

OBJECTIVE: To investigate if early variation of PET-derived parameters after concomitant chemoradiotherapy (CRT) predicts overall survival (OS), local relapse free survival (LRFS), distant relapse free survival (DRFS) and progression free survival (PFS) in locally advanced pancreatic cancer (LAPC) patients. METHODS: Fifty-two LAPC patients (median age: 61 years; range: 35-85) with available FDG PET/CT before and after RT (2-6 months, median: 2) were enrolled from May 2005 to June 2015. The predictive value of the percentage variation of mean/maximum standard uptake value (ΔSUVmean/max), metabolic tumour volume (ΔMTV) and total lesion glycolysis (ΔTLG), estimated considering different uptake thresholds (40-50-60%), was investigated between pre- and post-RT PET. The percentage difference between gastrointestinal cancer-associated antigen (ΔGICA) levels measured at the time of PET was also considered. Log-rank test and Cox regression analysis were performed to assess the prognostic value of considered PET-derived parameters on survival outcomes. RESULTS: The median follow-up was 13 months (range: 4-130). At univariate analysis, ΔTLG50 showed borderline significance in predicting OS (P = 0.05) and was the most significant parameter correlated to LRFS and PFS (P = 0.001). Median LRFS was 4 and 33 months if ΔTLG50 was below or above 35% respectively (P = 0.0003); similarly, median PFS was 3 vs 6 months (P = 0.0009). No significant correlation was found between PET-derived parameters and DRFS, while the ΔGICA was the only borderline significant prognostic value for this endpoint (P = 0.05). CONCLUSION: PET-derived parameters predict survival in LAPC patients; in particular, ΔTLG50 is the strongest predictor. The combination of these biochemical and imaging biomarkers is promising in identifying patients at higher risk of earlier relapse.

Accurate outcome prediction after neo-adjuvant radio-chemotherapy for rectal cancer based on a TCP-based early regression index.

BACKGROUND AND PURPOSE: An early tumor regression index (ERITCP) was previously introduced and found to predict pathological response after neo-adjuvant radio-chemotherapy of rectal cancer. ERITCP was tested as a potential biomarker in predicting long-term disease-free survival. MATERIALS AND METHODS: Data of 65 patients treated with an early regression-guided adaptive boosting technique (ART) were available. Overall, loco-regional relapse-free and distant metastasis-free survival (OS, LRFS, DMFS) were considered. Patients received 41.4 Gy in 18 fractions (2.3 Gy/fr), including ART concomitant boost on the residual GTV during the last 6 fractions (3 Gy/fr, Dmean: 45.6 Gy). Chemotherapy included oxaliplatin and 5-fluorouracil (5-FU). T2-weighted MRI taken before (MRIpre) and at half therapy (MRIhalf) were available and GTVs were contoured (Vpre, Vhalf). The parameter ERITCP = -ln[(1 - (Vhalf/Vpre))Vpre] was calculated for all patients. Cox regression models were assessed considering several clinical and histological variables. Cox models not including/including ERITCP (CONV_model and REGR_model respectively) were assessed and their discriminative power compared. RESULTS: At a median follow-up of 47 months, OS, LRFS and DMFS were 94%, 95% and 78%. Due to too few events, multivariable analyses focused on DMFS: the resulting CONV_model included pathological complete remission or clinical complete remission followed by surgery refusal (HR: 0.15, p = 0.07) and 5-FU dose >90% (HR: 0.29, p = 0.03) as best predictors, with AUC = 0.75. REGR_model included ERITCP (HR: 1.019, p < 0.0001) and 5-FU dose >90% (HR: 0.18, p = 0.005); AUC was 0.86, significantly higher than CONV_model (p = 0.05). Stratifying patients according to the best cut-off value for ERITCP and to 5-FU dose (> vs <90%) resulted in 47-month DMFS equal to 100%/69%/0% for patients with two/one/zero positive factors respectively (p = 0.0002). ERITCP was also the only variable significantly associated to OS (p = 0.01) and LRFS (p = 0.03). CONCLUSION: ERITCP predicts long-term DMFS after radio-chemotherapy for rectal cancer: an independent impact of the 5-FU dose was also found. This result represents a first step toward application of ERITCP in treatment personalization: additional confirmation on independent cohorts is warranted.