Radioembolisation with <Superscript>90</Superscript>Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

Introduction  Radioembolisation with ⁹⁰Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients’ dosimetric data were reviewed according to the linear–quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Materials and methods  Twenty patients with metastatic lesions underwent radioembolisation. The ⁹⁰Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β = 2.5 Gy (NTL), 10 Gy (tumours); T _1/2,eff = T _1/2,phys = 64.2 h; T _1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. Results  In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9–3.2) GBq, tumour dose was 130 (65–235) Gy, and tumour BED was 170 (75–360) Gy. Considering two cycles, ∼15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10–35) Gy; tumour BED increase was 10 (3–11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ∼50 Gy (two cycles) and 65 Gy (three cycles). Conclusions  From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested.     

Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0–67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10–390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.     

Experimental stereotactic irradiation of normal rabbit lung: computed tomographic analysis of radiation injury and the histopathological features

Purpose The aim of this study was to establish an animal experimental model of pulmonary stereotactic irradiation and clarify the morphological patterns of pulmonary radiation injury with computed tomography and the histopathological features. Materials and methods Tiny spherical regions in the lungs of seven anesthetized rabbits were irradiated stereotactically with a single fractional dose of 21–60 Gy. Subsequently, the irradiated lungs were observed biweekly with computed tomography (CT) for 24 weeks. Radiation injury of the lung was examined histopathologically in one specimen. Results Localized hypodense changes were observed 7–15 weeks after irradiation in three rabbits irradiated with 60 Gy, and the findings persisted beyond that time. The electron density ratios in the lung fields obtained from the CT images were shown to be decreasing, corresponding to the hypodensity changes. No clear increased density opacity was observed in any rabbit in the 60-Gy irradiated group. Severe localized fibrotic change was observed in the histopathological specimens. Conclusion Specific localized hypodensity changes were found in only three rabbits irradiated with 60 Gy, the highest dose we employed.     

Patients undergoing recurrent CT scans: assessing the magnitude

To assess percent of patients undergoing multiple CT exams that leads to cumulative effective dose (CED) of ≥ 100 mSv and determine their age distribution. Data was retrieved retrospectively from established radiation dose monitoring systems by setting the threshold value of 100 mSv at four institutions covering 324 hospitals. The number of patients with CED ≥ 100 mSv only from recurrent CT exams during a feasible time period between 1 and 5 years was identified. Age and gender distribution of these patients were assessed to identify the magnitude of patients in the relatively lower age group of ≤ 50 years. Of the 2.5 million (2,504,585) patients who underwent 4.8 million (4,819,661) CT exams during the period of between 1 and 5 years, a total of 33,407 (1.33%) patients received a CED of ≥ 100 mSv with an overall median CED of 130.3 mSv and maximum of 1185 mSv. Although the vast majority (72–86%) of patients are > 50 years of age, nearly 20% (13.4 to 28%) are ≤ 50 years. The minimum time to accrue 100 mSv was a single day at all four institutions, an unreported finding to date. We are in an unprecedented era, where patients undergoing multiple CT exams and receiving CED ≥ 100 mSv are not uncommon. While underscoring the need for imaging appropriateness, the consideration of the number and percent of patients with high exposures and related clinical necessities creates an urgent need for the industry to develop CT scanners and protocols with sub-mSv radiation dose, a goal that has been lingering. • We are in an era where patients undergoing multiple CT exams during a short span of 1 to 5 years are not uncommon and a sizable fraction among them are below 50 years of age. • This leads to cumulative radiation dose to individual patients at which radiation effects are of real concern. • There is an urgent need for the industry to develop CT scanners with sub-mSv radiation dose, a goal that has been lingering.     

Automated CT volumetry of pulmonary metastases: the effect of a reduced growth threshold and target lesion number on the reliability of therapy response assessment using RECIST criteria

The purpose of this study was to evaluate the reproducibility of CT-volumetric tumour response assessment of pulmonary metastasis using variable volume change thresholds (VCT) and target lesions with response evaluation criteria in solid tumours (RECIST). Fifty consecutive patients with pulmonary metastases undergoing follow-up multislice CT under chemotherapy were assessed for response to chemotherapy with modifications to RECIST: (1) decreasing the percentual VCT for diagnosis of tumour response (range = 70%–20%), (2) reducing the number of target lesions (range = 1–5). Continuous and categorical observer agreements were tested by Bland and Altman and extended (κ_e) or non-weighted kappa (κ) and correlated with percentual VCT to predict observer agreement. A total of 202 metastases were evaluated (average volume = 522.4 mm³±902.4 mm³). General agreement on treatment response was very high (κ_e = 0.93–1), but was reduced with VCT < 35% (κ_e < 0.95). Kappa correlation with VCT values was strong (r=0.94–0.96; p≤0.0002). Average confidence decreased significantly at VCT < 45% (p < 0.01) and agreement on stable disease at VCT < 35% (κ_e < 0.95; p < 0.01). Reduction of target lesions (n < 3; VCT = 35%) resulted in decreased reader confidence (for n = 1: κ = 0.49; p < 0.05). Agreement for evaluation of treatment response was robust using VCT ≥35% and ≥3 metastases. This may translate into shortening of follow-up intervals or enable for response assessment with tumours displaying minimal volume change.     

Clinical outcome of stereotactic body radiotherapy of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system

Purpose The aim of this study was to investigate the clinical outcome of stereotactic body radiotherapy (SBRT) of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system. Methods and materials The subjects were 19 patients who had localized lung tumor (11 primaries, 8 metastases) between May 2003 and October 2005. Treatment was conducted on 19 lung tumors by fixed multiple noncoplanar conformal beams with a standard linear accelerator. The isocentric dose was 54 Gy in nine fractions. The median overall treatment time was 15 days (range 11–22 days). All patients were immobilized by a thermo-shell and a custom-made headrest during the treatment. Results The crude local tumor control rate was 95% during the follow-up of 9.4–39.5 (median 17.7) months. In-field recurrence was noted in only one patient at the last follow-up. The Kaplan-Meier overall survival rate at 2 years was 89.5%. Grade 1 radiation pneumonia and grade 1 radiation fibrosis were observed in 12 of the 19 patients. Treatment-related severe early and late complications were not observed in this series. Conclusion The stereotactic body radiotherapy of 54 Gy in nine fractions achieved acceptable tumor control without any severe complications. The results suggest that SBRT can be one of the alternatives for patients with localized lung tumors. Part of this work was presented at the 65th annual meeting of the Japan Radiological Society, April 2006     

Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas

Purpose The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics—fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)—can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT). Methods and materials Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis. Results Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins > 55 Gy and 50–55 Gy. For the 45–50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the >55 Gy and 50–55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT. Conclusion Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a thresh-old dose of 45–50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50–55 Gy and >55 Gy, thus providing an objective measure of radiation effect on NAWM.     

Yield of head CT in the alcohol-intoxicated patient in the emergency department

We aimed to determine the yield of positive head computed tomography (CT) findings among suspected alcohol-intoxicated patients presenting to the emergency department (ED). Our secondary aim was to determine if elderly intoxicated patients were more likely to have an intracranial injury. We identified patients suspected of alcohol intoxication who underwent CT scanning in the ED over a 4-year period. Pre-determined data elements including demographics, diagnosis, and disposition were extracted using a pre-formatted data sheet by blinded abstractors. “Positive” CT was defined as evidence of any type of intracranial hemorrhage. A total of 2,671 subjects with suspected alcohol intoxication and a head CT were identified. Fifty out of the 2,671 (1.9%) had a positive CT. Among CT scans of elderly (≥60 years of age) subjects, 15/555 (2.7%, 95% CI = 1.4–4.1%) were positive compared with 35/2,116 (1.7%, 95% CI = 1.1–2.2%) among those <60 years of age (p = 0.11). The yield of positive head CT among alcohol-intoxicated patients was low, at 1.9%. An age cutoff of 60 years in this population did not predict a significantly higher positive rate.     

Explanation for the failure of neoadjuvant chemotherapy to improve outcomes after radiotherapy for locally advanced uterine cervical cancer from the standpoint of the tumor regression rate

Purpose Treatment outcomes for patients with locally advanced cervical cancer are no better with neoadjuvant chemotherapy (NAC) combined with radiotherapy (RT) than with RT alone. We investigated the reason for this failure from the standpoint of the tumor regression rate (RR). Materials and methods A total of 48 patients with clinical stage IIB-IVA cervical squamous cell carcinoma were treated clinically with cisplatin-based NAC plus RT (n = 15) or RT alone (n = 33). The RR was defined as the slope of a tumor shrinkage curve derived with magnetic resonance images. The local control rate (LCR) and disease-free rate (DFR) were estimated by clinical stage (IIB vs. III-IVA), pretreatment volume (≤ median vs. > median), lymph node status (negative vs. positive), treatment type, overall treatment time (≤8 weeks vs. >8 weeks), and RR (≤ median vs. > median) using univariate and multivariate analyses. Results RR during NAC or during NAC and RT (n = 15) was not significantly higher than RR by RT alone (n = 33). Low RR and positive nodal status were significantly powerful prognostic factors for both the LCR and DFR, whereas the others were not. Conclusion Although effective in reducing tumor volume prior to RT, NAC showed no overall effect in increasing the RR, which was shown to be the most powerful prognostic factor. Part of this study was presented at the 17th International Congress on Anti-Cancer Treatment (January 30–February 2, 2006, Paris) and the 65th Annual Meeting of the Japan Radiological Society (April 7–9, 2006, Yokohama)     

High-dose-rate brachytherapy for previously irradiated patients with recurrent esophageal cancer

Purpose Our objective was to assess the feasibility, efficacy, and complications of high-dose-rate (HDR) brachytherapy for patients with recurrent esophageal cancer after external radiotherapy. Materials and methods Six patients with recurrent esophageal cancer after external radiotherapy were treated with HDR brachytherapy (Ir-192 source) from January 2003 to February 2004. The median age of the patients was 69 years. All patients had received external radiotherapy (median dose 60 Gy) before HDR brachytherapy. All patients underwent HDR brachytherapy once a week with a dose of 4 or 5 Gy per fraction in the esophageal mucosa (median total dose 20 Gy). The Kaplan-Meier method was used to calculate local control rates. Results The median overall survival period was 30.0 months. Local control was observed in five patients and residual tumor in one patient. Persistent local control was observed in two patients. No patient died of esophageal cancer, and all patients survived. We observed no severe late complications related to HDR brachytherapy. Conclusion These data suggest that HDR brachytherapy is an effective and safe treatment for patients with recurrent esophageal cancer after external radiotherapy.     

Effects of postmortem positional changes on conjunctival petechiae

The present study aimed to determine whether postmortem period, physical constitution, cause of death, and cardiopulmonary resuscitation are associated with positional changes in the postmortem appearance of conjunctival petechiae. We retrospectively investigated serial forensic autopsies from 6 h to 6 days postmortem (n = 442; male, 303; female, 139; median age, 62 years; range, 0–100 years). The causes of death were sharp instrument injury, blunt force trauma, fire, intoxication, asphyxia, drowning, hypothermia, hyperthermia, acute heart failure, and natural causes. Of these, 28 (male, n = 18; female, n = 10) were aged ≤5 years. Palpebral conjunctival petechiae were initially assessed at autopsy in supine bodies, then reassessed in prone bodies after 30 min. Among 414 bodies, 291 (70.2%) and 123 (29.7%) who were aged between 6 and 100 years, and 18 (64.2%) and 10 (35.7%) aged <5 years at the time of death, were discovered in the supine and prone positions, respectively. The amounts of petechiae increased within 1.5 days postmortem, but not in those discovered in the prone position. The rates at which petechiae increased were higher in supine overweight bodies (BMI ≥ 25.0) and in those who were discovered supine and had died of asphyxia or drowning (37.5%). Cardiopulmonary resuscitation for bodies discovered in the supine and prone positions did not statistically affect the occurrence of petechiae. Several postmortem factors can cause hypostatic blood redistribution that manifests as increased amounts of petechiae in the palpebral conjunctivae.     

Diffusion tensor imaging: the normal evolution of ADC,RA, FA,and eigenvalues studied in multiple anatomical regions of the brain

Introduction  The aim of our work was to investigate the process of myelination in healthy patients using the diffusion parameters apparent diffusion coefficient (ADC), relative anisotropy (RA), fractional anisotropy (FA), and eigenvalues. Age-dependent changes were assessed using the slope m of the fit functions that best described the data. Materials and methods  Seventy-two patients (3 weeks–19 years) without pathological magnetic resonance imaging findings were selected from all pediatric patients scanned with diffusion tensor imaging over a 5-year period at our institution. ADC, RA, FA, and eigenvalue maps were calculated and regions of interest were selected in anterior/posterior pons, genu/splenium of corpus callosum (CC), anterior/posterior limb of internal capsule (IC), and white matter (WM) regions (frontal, temporal, parietal, occipital WM). Statistical analysis was performed using Spearman correlation coefficient and regression analysis. Results  Mean values ranged 71.6 × 10⁻⁵ to 90.3 × 10⁻⁵ mm²/s (pons/parietal WM) for ADC, 0.32–0.94 (frontal WM/CC) for RA, and 0.36–0.81 (frontal WM/splenium) for FA. Logarithmic fit functions best described the data. Strong age influences were observed for CC, pons, and parietal/frontal WM and changes were significant for all three eigenvalues, most pronounced for perpendicular eigenvalues. Changes in RA and FA differed depending on the structure anisotropy. Conclusions  Changes observed for ADC, RA, FA, and eigenvalues with age were consistent with previous findings. Changes detected for RA and FA varied due to the different scaling of both parameters. We found that the use of the largely linear scaled RA adds more valuable information for the assessment of age-dependent structural changes as compared to FA. Additionally, we report normative values for the diffusion parameters studied.     

CT colonography: optimisation,diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging

To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography (CTC). Ninety-five subjects underwent reduced-laxative (13 g senna/18 g magnesium citrate) CTC prior to same-day colonoscopy and were randomised to one of four tagging regimens using 20 ml 40%w/v barium sulphate: regimen A: four doses, B: three doses, C: three doses plus 220 ml 2.1% barium sulphate, or D: three doses plus 15 ml diatriazoate megluamine. Patient experience was assessed immediately after CTC and 1 week later. Two radiologists graded residual stool (1: none/scattered to 4: >50% circumference) and tagging efficacy for stool (1: untagged to 5: 100% tagged) and fluid (1: untagged, 2: layered, 3: tagged), noting the HU of tagged fluid. Preparation was good (76–94% segments graded 1), although best for regimen D (P = 0.02). Across all regimens, stool tagging quality was high (mean 3.7–4.5) and not significantly different among regimens. The HU of layered tagged fluid was higher for regimens C/D than A/B (P = 0.002). Detection of cancer (n = 2), polyps ≥6 mm (n = 21), and ≤5 mm (n = 72) was 100, 81 and 32% respectively, with only four false positives ≥6 mm. Reduced preparation was tolerated better than full endoscopic preparation by 61%. Reduced-laxative CTC with three doses of 20 ml 40% barium sulphate is as effective as more complex regimens, retaining adequate diagnostic accuracy.     

Cartilage lesions of the glenohumeral joint: diagnostic effectiveness of multidetector spiral CT arthrography and comparison with arthroscopy

This study assessed the diagnostic effectiveness of multidetector spiral CT arthrography (MDCTa) in detecting hyaline cartilage abnormalities of the shoulder joint, with correlation to arthroscopy. Shoulder MDCTa images prospectively obtained in 22 consecutive patients (mean age, 50 years; age range, 23–74 years; 12 female, 10 male) were evaluated for glenohumeral cartilage lesions. Two musculoskeletal radiologists independently analysed the cartilage surfaces of the humeral head and of the glenoid fossa in nine anatomical surface areas. Observations of MDCTa were compared to arthroscopic findings. The sensitivity and specificity of MDCTa for grade 2 (substance loss <50%) or higher and grade 3 (substance loss ≥50%) or higher cartilage lesions, the Spearman correlation coefficient between arthrographic and arthroscopic grading, and K statistics for assessing Intra and Interobserver reproducibility were determined. At MDCTa, sensitivities and specificities ranged between 80% and 94% for the detection of grade 2 or higher cartilage lesions, and between 88% and 98% for the detection of grade 3 or higher cartilage lesions. Spearman correlation coefficients between MDCTa and arthroscopic grading of articular surfaces ranged between 0.532 and 0.651. Interobserver agreement was moderate for grading all articular surfaces (κ = 0.457), but substantial to almost perfect for detecting lesions with substance loss (κ, 0.618–0.876). In conclusion, MDCTa is accurate for the study of cartilage surface in the entire shoulder joint. This technique may beneficially impact patient’s management by means of selecting the proper treatment approach.     

Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with <Superscript>90</Superscript>Y-DOTATOC and <Superscript>177</Superscript>Lu-DOTATATE: the role of associated risk factors

Purpose  Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE is promising. The kidney is the critical organ and despite renal protection, function loss may become evident years later. The aim of this study was to analyse renal parameters in patients who had undergone dosimetry before PRRT. Methods  Among those in protocols at our institution, 28 patients were considered: 23 received ⁹⁰Y-DOTATOC (3.8–29.2 GBq, median 12.2) and five received ¹⁷⁷Lu-DOTATATE (20.7–29.2 GBq, median 23.2). Patients were followed up after therapy for creatinine and creatinine clearance loss (CCL) for 3–97 months (median 30). Renal doses and bio-effective doses (BED) were calculated (MIRD, LQ model). Results  After ⁹⁰Y-DOTATOC toxicity on creatinine according to NCI criteria occurred in nine cases (seven grade 1, one grade 2, one grade 3), CCL at 1 year was >5% in 12 cases and >10% in eight. A 28-Gy BED threshold was observed in patients with risk factors (mainly hypertension and diabetes), while it was 40 Gy in patients without risk factors. Probably due to the low number of patients, despite the absence of severe toxicity after hyper-fractionated PRRT, clear correlations between fractionation and toxicity could not be found. After ¹⁷⁷Lu-DOTATATE, no toxicity occurred in 1–2 year follow-up; CCL at 1 year >5% occurred in three patients and >10% in two. Conclusions  Our results indicate the importance of clinical screening for risk factors: In this case, a BED <28 Gy is recommended. Fractionation of therapy is important in order to decrease toxicity, and further studies are needed to evaluate its clinical impact. An erratum to this article can be found at     

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4–5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1–3, 3–5, 5–8, 8–10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 ± 0.28 years (95% CI: 2.25–3.35) and 4.28 ± 0.40 years (95% CI: 3.51–5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate. Supported by the National Key Medical Research and Development Program of China during the 9th Five-year Plan Period (no. 96–907–03–04), Shanghai Nature Science Funds (no. 02Z1314073), Shanghai Medical Development Funds (no. 00419), the National Natural Science Foundation of China (no. 30670614).     

Acute and late genitourinary toxicity of conformal radiotherapy for prostate cancer

Purpose The aim of this study was to identify predictive factors for genitourinary (GU) toxicity in prostate cancer patients who underwent conformal radiotherapy (CRT). Materials and methods In this study we analyzed 154 cases of T1-3N0M0 prostate adenocarcinoma and evaluated the occurrence rate of acute and late GU toxicity and the duration of acute toxicity according to clinical parameters: age, transurethral resection of the prostate prior to CRT, hormone therapy, CRT dose, length of planning target volume (PTV). Results Altogether, 41% of the patients developed grade 2 or higher acute GU toxicity. Longer PTV was significantly associated with a higher incidence of acute GU toxicity (>7 cm, 53%; ≤7 cm, 31%; P = 0.003), and hormone therapy prolonged the duration of the toxicity (P = 0.007). Grade 1 or higher late GU toxicity developed in 23% of the patients, and the 2-year late GU toxicity-free survival rate was 79%. Acute GU toxicity was significantly associated with the late GU toxicity-free survival rate (grade 0–1, 88.7%; grade 2–4, 73.2%; P = 0.0007). Conclusion The length of PTV and hormone therapy were predictive factors for acute GU toxicity. Furthermore, acute GU toxicity was the most important predictive factor for late GU toxicity.     

Clinical and radiological outcomes of acute ischemic stroke patients without angiographic occlusion on digital subtraction angiogram. A pooled analysis of case series

Introduction  Approximately 20–30% of the patients with acute ischemic stroke do not have any occlusion demonstrated on initial digital subtraction angiography (DSA). We sought to determine the risk and rates of cerebral infarction and favorable neurological outcome in this group of acute ischemic stroke patients. Materials and methods  Patients were identified from a prospectively maintained stroke database and from literature search of MEDLINE, PubMed, and Cochrane databases. All patients had initial neurological assessment on National Institutes of Health Stroke Scale (NIHSS). Patients then underwent DSA after initial head computed tomography (CT) scans. Follow-up radiological assessment at 24–72 h was performed with CT and magnetic resonance imaging scans. Association of stroke risk factors with clinical and radiological outcomes was estimated. Results  A total of 81 patients was analyzed (mean age 63 years; 28 were women). The median NIHSS score was 8 (range 2–25). None of the patients received either intravenous or intra-arterial thrombolytic. Cerebral infarction was detected in 62 (76%) of the 81 patients. Twenty-four to 48-h NIHSS was available for 51 patients only. Neurological improvement was observed in 22 (43%) of the 51 patients. Favorable outcome ascertained at 3-month follow-up was seen in 48 (59%) of the 81 patients. After adjusting for age, sex, and baseline NIHSS, male patients [odds ratio (OR) 4.5 (1.4–14.3), p value = 0.01] and patients with age ≥65 [OR 4.3 (1.2–16.2), p value = 0.03] have a higher risk of cerebral infarcts on the follow-up imaging. Similarly, patients who presented with <10 NIHSS had a better 3-month outcome than those with >10 NIHSS [OR 0.21 (0.08–0.61), p value = 0.004]. Conclusion  Ischemic stroke patients without arterial occlusion on DSA have a higher risk of cerebral infarction and disability particularly in men, patients over 65 years of age and with NIHSS ≥10. The cause of infarction may have been arterial obstruction with spontaneous recanalization or small vessel occlusion not visible on DSA.     

Correlation of volumetric mismatch and mismatch of Alberta Stroke Program Early CT Scores on CT perfusion maps

Introduction  We aimed to determine if volumetric mismatch between tissue at risk and tissue destined to infarct on computed tomography perfusion (CTP) can be described by the mismatch of Alberta Stroke Program Early CT Score (ASPECTS). Materials and methods  Forty patients with nonlacunar middle cerebral artery infarct <6 h old who had CTP on admission were retrospectively reviewed. Two raters segmented the lesion volume on mean transit time (MTT) and cerebral blood volume (CBV) maps using thresholds of >6 s and <2.0 mL per 100 g, respectively. Two other raters assigned ASPECTS to the same MTT and CBV maps while blinded to the volumetric data. Volumetric mismatch was deemed present if ≥20%. ASPECTS mismatch (=CBV ASPECTS − MTT ASPECTS) was deemed present if ≥1. Correlation between the two types of mismatches was assessed by Spearman’s coefficient (ρ). ROC curve analyses were performed to determine the optimal ASPECTS mismatch cut point for volumetric mismatch ≥20%, ≥50%, ≥100%, and ≥150%. Results  Median volumetric mismatch was 130% (range 10.9–2,031%) with 31 (77.5%) being ≥20%. Median ASPECTS mismatch was 2 (range 0–6) with 26 (65%) being ≥1. ASPECTS mismatch correlated strongly with volumetric mismatch with ρ = 0.763 [95% CI 0.585–0.870], p < 0.0001. Sensitivity and specificity for volumetric mismatch ≥20% was 83.9% [95% CI 65.5–93.5] and 100% [95% CI 65.9–100], respectively, using ASPECTS mismatch ≥1. Volumetric mismatch ≥50%, ≥100%, and ≥150% were optimally identified using ASPECTS mismatch ≥1, ≥2, and ≥2, respectively. Conclusion  On CTP, ASPECTS mismatch showed strong correlation to volumetric mismatch. ASPECTS mismatch ≥1 was the optimal cut point for volumetric mismatch ≥20%.     

Three-dimensional Monte Carlo-based voxel-wise tumor dosimetry in patients with neuroendocrine tumors who underwent 177 Lu-DOTATOC therapy

Patients with advanced neuroendocrine tumors (NETs) of the midgut are suitable candidates for 177Lu-DOTATOC therapy. Integrated SPECT/CT systems have the potential to help improve the accuracy of patient-specific tumor dosimetry. Dose estimations to target organs are generally performed using the Medical Internal Radiation Dose scheme. We present a novel Monte Carlo-based voxel-wise dosimetry approach to determine organ- and tumor-specific total tumor doses (TTD). A cohort of 14 patients with histologically confirmed metastasized NETs of the midgut (11 men, 3 women, 62.3 ± 11.0 years of age) underwent a total of 39 cycles of 177Lu-DOTATOC therapy (mean 2.8 cycles, SD ± 1 cycle). After the first cycle of therapy, regions of interest were defined manually on the SPECT/CT images for the kidneys, the spleen, and all 198 tracer-positive tumor lesions in the field of view. Four SPECT images, taken at 4 h, 24 h, 48 h and 72 h after injection of the radiopharmaceutical, were used to determine their effective half-lives in the structures of interest. The absorbed doses were calculated by a three-dimensional dosimetry method based on Monte Carlo simulations. TTD was calculated as the sum of all products of single tumor doses with single tumor volumes divided by the sum of all tumor volumes. The average dose values per cycle were 3.41 ± 1.28 Gy (1.91–6.22 Gy) for the kidneys, 4.40 ± 2.90 Gy (1.14–11.22 Gy) for the spleen, and 9.70 ± 8.96 Gy (1.47–39.49 Gy) for all 177Lu-DOTATOC-positive tumor lesions. Low- and intermediate-grade tumors (G 1–2) absorbed a higher TTD compared to high-grade tumors (G 3) (signed-rank test, p =  < 0.05). The pre-therapeutic chromogranin A (CgA) value and the TTD correlated significantly (Pearson correlation:  = 0.67, p = 0.01). Higher TTD resulted in a significant decrease of CgA after therapy. These results suggest that Monte Carlo-based voxel-wise dosimetry is a very promising tool for predicting the absorbed TTD based on histological and clinical parameters.