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Related Blogs
IoT Trends of 2020 That Will Reinvent Everything
We are currently living in a world that is managed …

subset: commoncrawl


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Editorial: Godspeed, Commissioner Portune; boycotting Kroger Co. is a bad idea
Enquirer editorial board
In this weekly column, The Enquirer editorial board celebrates successes across our region and calls out those who stand in the way of progress.
Thumbs up
- Godspeed to Hamilton County Commissioner Todd Portune as he prepares to undergo leg amputation surgery Monday morning at Ohio State. The 59-year-old Green Township resident announced Wednesday he has been diagnosed with cancer in his left leg. In addition to being a dedicated and hard-working elected official, Portune is a resilient fighter and eternal optimist who has overcome significant health challenges in the past. There is no reason to think he can't do it again. Our thoughts and prayers go out to Portune and his family and we wish him a speedy recovery.
- New jobs are always good news, especially when they are coming from one of the region's top employers. Kroger said it will hire 11,000 new workers this year, including 500 in Greater Cincinnati and Northern Kentucky. This on the heels of the grocer's labor agreement with the UFCW 75 that was ratified last month and set the stage for a higher starting wage of $10 per hour in the Cincinnati/Dayton division. Kroger officials said they will also unveil this month specifics on how the company will invest tax cuts signed into law by President Donald Trump to benefit workers. Higher wages and more jobs coming to Cincinnati is a winning combo.
- More Hamilton County babies seeing their first birthday is cause for celebration. Cradle Cincinnati deserves a great deal of credit for the turnaround in the county's infant mortality rate, which is one of the worst in the nation. In Hamilton County, an average of 97 babies have died in each of the past five years, down from an average of 115 deaths between 2008 and 2012. Cradle Cincinnati reports more pregnant mothers have stopped smoking, and more of them carry their babies to term. Avondale, which had one of the highest rates of infant mortality in the county, has had no babies die from a preterm birth between 2015 and 2017. Those results were so impressive the Ohio Department of Health has pledged an additional $850,000 to expand Cradle Cincinnati's programming to Winton Hills and North College Hill.
Thumbs down
- The mess involving City Manager Harry Black just got messier. A week ago, Cincinnati City Council looked to be on the cusp of solving the public feud between Black and Mayor John Cranley when it agreed to terms on a method of investigating the manager. However, council has been sued twice since then. The Enquirer filed suit because of the proposed format for the investigation, which includes two council members interviewing city employees privately, a possible violation of the city's charter. The other suit was filed by resident Mark Miller who alleges five members of City Council held illegal, secret meetings via text and email to discuss Cranley's request that Black resign. While this City Hall circus certainly isn't lacking for sideshows, it's been anything but entertaining for taxpayers and city employees. Council needs to find a transparent and legal way to wrap this sad chapter up as quickly as possible.
- Civil rights icon, the Rev.Jesse Jackson, came to Cincinnati this week to encourage the expansion of a boycott against Kroger for creating "food deserts" by closing stores in low-income African-American and white neighborhoods. The topic of food deserts is a serious and important one, worthy of discussion and attention, and we thank Rev. Jackson for casting a spotlight on the need. However, boycotting one of the region's largest employers is not the most effective way to solve the problem. Kroger has been a good community partner through the years. We're sure there are more collaborative ways to get the grocer at the table to discuss reasonable solutions to this dilemma than threats of a nationwide boycott.
- Democratic gubernatorial candidate Bill O'Neill probably should expect to win too many votes in Cincinnati after his major flub at Tuesday night's primary debate. When asked a question about the Brent Spence Bridge project, O'Neill drew a blank. "I don't know about your bridge," O'Neill said. You don't know about the bridge? We don't know about your chances of winning the primary, Mr. O'Neill, at least not in this neck of the woods. Try doing your homework next time. That tends to show voters that you have a clue and care about the issues that matter most to them.
Opinion Editor Kevin S. Aldridge writes this on behalf of the editorial board which includes, President Eddie Tyner, Executive Editor Beryl Love, Senior News Director Michael McCarter, Audience Engagement Editor Katie Vogel and Columnist Byron McCauley. He can be reached at firstname.lastname@example.com. Twitter: @kevaldrid.


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- Research
- Open Access
- Published:
External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26
Radiation Oncology volume 12, Article number: 12 (2017)
1464 Accesses
5 Citations
1 Altmetric
To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC).
Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if ≥90% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54–70Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5. Primary trial endpoint was dose-limiting toxicity (DLT), as specifically defined for 17 clinical and nine laboratory parameters as grade ≥3 or ≥4 toxicity (CTCAE vs. 3). The threshold to declare a dose level as maximum tolerated dose (MTD) was defined as a DLT rate of ≤16.7% in dose levels 1–3, and ≤10% in dose levels 4–5. Best objective response of target liver lesions and adverse events (AE's) were assessed as secondary endpoints.
The trial was terminated early in DL 3 due to low accrual. Nineteen patients were recruited. Fifteen patients were evaluable for the primary and 18 for the secondary endpoints. Maximum tolerated dose was not reached. One patient in dose level 1, and one patient in dose level 2 experienced DLT (lipase > 5xULN, and neutrophils <500/μL respectively). However, dose level 3 (62Gy) was completed, with no DLTs in 3 patients.
Overall, 56% of patients had a partial response and 28% showed stable disease according to RECIST. No signs of radiation induced liver disease (RILD). Two patients in dose level 3 experienced lymphocytopenia grade 4, with no clinical impact.
Conventionally fractionated radiotherapy of 58Gy to even large HCC was safe for patients with CPS A and B. 62Gy was delivered to three patients without any sign of clinically relevant increased toxicity. The maximum tolerated dose could not be determined.
Trial registration
ClinicalTrials.gov identifier NCT00777894, registered October 21st, 2008.
Hepatocellular carcinoma is the most common primary liver tumor and the 2nd leading cause of cancer related mortality worldwide. It represents 7% of all diagnosed cancers and its overall 5-year survival rate < 12%. In Europe, liver cirrhosis patients progress to HCC at a conversion rate of approximately 3% per year in Europe [1]. Prior to intensity-modulated radiotherapy (IMRT) or stereotactic body radiotherapy (SBRT), use of external beam radiotherapy (RT) has been quite limited in the treatment of HCC [2]. The whole liver has a low tolerance to radiation and patients are at risk for unacceptable liver toxicity [3]. Radiation injury to the liver after conventionally fractionated radiotherapy (cfRT), was first described by Ingold et al. several decades ago [4]. The clinical scenario of radiation induced liver disease RILD consists of anicteric hepatomegaly, ascites, and elevated alkaline phosphatase [5]. In the landmark report by Emami et al. [3], the whole-liver tolerance dose (TD) expected to yield a 5% risk of liver failure 5 years after treatment (TD 5/5) for whole-liver radiation was estimated to be 30Gy in 2Gy fractions. The Lyman normal tissue complication probability (NTCP) model and a local damage-organ injury NTCP model later have been used to describe the partial tolerance of the liver to RT [6]. Image-guided volumetric arc therapy (VMAT), IMRT and SBRT dose delivery, allow reducing the dose to non-tumor liver tissue, kidneys and the intestines. Thus, dose escalation to the diseased liver segments has become possible. This trial was conducted to obtain better understanding of the RT dose-response-relationship for tumor control as well as for normal tissue toxicities in this patient group. We report the results of the Swiss Group for Clinical Cancer Research (SAKK) 77/07 phase I trial assessing feasibility and safety of cfRT in patients with locally advanced non-resectable HCC.
Patients and Methods
Patients with unresectable, histologically or radiologically confirmed stage cT1–4, cN0–1 HCC, Barcelona clinic liver cancer (BCLC) stage B and C with no prior malignancy within 5 years were eligible for this phase I trial. Patients had to be older than 18 years, with a Child-Pugh A or B score, with a residual liver volume (= total liver volume – the gross tumor volume (GTV)) of >800 ml and ≥40% of uninvolved liver and WHO performance status 0–2. Metastatic HCC was allowed if ≥90% of total tumor volume was located within the liver. Exclusion criteria included, ALT and AST ≥5x upper limit of normal (ULN), AP ≥ 5 x ULN, bilirubin ≥3 x ULN, hemoglobin ≤ 100 g/L, neutrophils ≤1.2 x 109/L, platelets ≤ 50 x 109/L, international normalized ratio (INR) >2, creatinine clearance ≤ 50 mL/min, clinical ascites, encephalopathy, active hepatitis, gastric, duodenal, or variceal bleeding or weight loss ≥ 15% within three months of registration or esophageal varices ≥ grade 3 [7, 8]. Patients were also excluded, if they had prior RT to the abdomen or caudal chest below T5, prior transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) within eight weeks. No chemotherapy was permitted within three weeks before registration. Portal vein thrombosis (PVTT) was not an exclusion criterion.
The study was planned and conducted in accordance with the principles of the Declaration of Helsinki. The protocol was approved by the ethics committee of each participating site (ClinicalTrials.gov identifier NCT00777894, registered October 21st, 2008). Written informed consent was obtained from all patients.
Radiation therapy
Pretreatment triphasic diagnostic computed tomography (CT) was used to delineate the gross tumor volume (GTV) and enhanced area of vessel thrombosis. Patients were treated in supine position. Respiratory gating or breath holding techniques were used. Triphasic CT simulation with intravenous contrast was used with a 3- to 5-mm-slice thickness. The range of the simulation CT scan included the whole liver, lower part of the lungs, and both kidneys. The GTV was defined as the visible tumor on the arterial phase of simulation CT and/or fused diagnostic CT. For patients with coexisting PVTT, the area of PVTT was included as a part of the GTV. The clinical target volume (CTV) encompassed the area of the GTV with a 5–10 mm margin. The CTV was expanded by a 5- to 10-mm radial margin and a 6- to 15-mm cranio-caudal margin to create the planning target volume (PTV). Normal liver was defined as the whole liver volume minus the PTV. Patients were treated with either 3D-conformal RT (3D-CRT), IMRT or fractionated stereotactic RT techniques, using 6–18 MV photon energies. Due to compatibility between centers, dose prescription and normalization were fixed at isocenter and for conformal therapy, according to the international commission on radiation units and measurements (ICRU) reports 50 and 62. In case of IMRT, dose prescription and normalization could be defined as mean dose to PTV for optimization reasons, but for reporting it was rescaled to the isocenter. No normalization/prescription to isodose levels was allowed. For 3D-conformal planning: 2 to 5 portal beams with planar or non-coplanar arrangement were used. Larger number of fields was allowed to use to improve the quality of dose distribution [9]. For adequate target coverage, the PTV received 95–107% of the prescribed total dose. Alternatively, a minimum of 95% of the prescribed dose had to encompass more than 99% of the PTV. In addition, it was recommended that areas receiving more than 105% of the prescribed dose, are kept to <1% of the PTV. Our protocol suggested that participants have >800 mL and > 40% of non-tumor liver and that the mean dose has to be kept < 28Gy in patients with a non-cirrhotic liver and < 24Gy in patients with signs of cirrhotic liver. If the PTV encompassed >66% of the total liver volume, radiotherapy was not initiated. RT was delivered from Monday to Friday in five fractions per week, of 2Gy per fraction to a total dose of 10Gy per week. Normal tissue dose delivery guidelines for bowel, stomach, esophagus (each Dmean < 40Gy, V60Gy <3%), lung (V5Gy <85%, V20Gy <20% and Dmean < 12–15Gy), heart (Dmean < 40Gy), spine (D1% <48Gy) and kidneys (Dmean left kidney <12Gy and if V50% of right kidney irradiated >20Gy, Dmean left kidney <5Gy) were provided to facilitate planning [10, 11].
Escalation strategy
Patients were to be enrolled onto five dose-escalation levels (54, 58, 62, 66 and 70Gy in 2Gy fractions, corresponding to a biological effective dose (BED) of 162, 174, 186, 198 and 210Gy with an alpha/beta ratio of 10, based on a modified 3 + 3 design. In dose levels 1 to 3, three patients, and in dose level 4 and 5, five patients had to be treated per cohort. Escalation to the next dose level was only permitted once no DLT was established within one month after the end of RT. If toxicity occurred in dose levels 1–3, a minimum of six patients and for dose level 4 and 5, a minimum of ten patients needed to be treated at that level, before escalating to the next level. While waiting until one month after RT, at which time the presence or absence of toxicity was determined, subsequent patients could be treated at the pre-defined dose level, up to a dose of 44Gy. DLT was specifically defined for 17 clinical and nine laboratory parameters as grade ≥3 or ≥4 toxicity according to CTCAE vs. 3. The threshold to declare a dose level as MTD, was defined, as a DLT rate of ≤16.7% in dose levels 1–3, and ≤10% in dose levels 4–5. A dose of 54Gy was chosen as the lowest dose level, because doses up to 54Gy showed response rates at around 50% [12].
Quality assurance (QA)
Before starting patient accrual, each participating center was required to successfully participate in a radiotherapy specific quality assurance (RT-QA) program corresponding to EORTC QART [13] levels 1 and 2: 1.) Facility questionnaire External dosimetry audit (EDA), 2.) dummy run (DR). For the DR an anonymized case including CT data set was made available. Target volumes (GTV, CTV, PTV) and all organs at risk (OAR) were delineated by the center's investigator and reviewed by the coordinating investigator. Deviations from the protocol were communicated to the participating center, and a revised version of the delineated structures was requested and reviewed. The approved structures were then used to elaborate a treatment plan using the RT technique chosen by the center. The plans were reviewed by the trial chair and trial medical physicist, which requested a revised version, in case of deviations from the protocol.
An internal report comparing the anonymized DR results of the first five participating centers was made available to those centers. Coincidence histograms [14] were used for a quantitative topological comparison of the delineated structures.
Patients were assessed weekly during RT, and after completion of treatment, followed up for one year at 1, 2, 3, 5, 8 and 11 months. At the first month follow-up physical examination, hemoglobin, neutrophils, platelets, hepatic function, renal function, pancreatic lipase, INR and CPS were reviewed. The reason for including pancreatic lipase in the follow up examination was to discover pancreatitis. Liver triphasic CT was performed at 2 and 5 months after RT, thereafter every 3 months until progression. At each follow-up within the first three months after RT, toxicity was graded using the CTCAE vs. 3. RILD was defined as the development of nonmalignant ascites without disease progression and an anicteric elevation of alkaline phosphatase level by at least twofold. Non – classic RILD was defined as the development of jaundice and/or elevated serum transaminases (>5 x UL) within 3 months of completion of RT in patients with underlying chronic hepatic disease (cirrhosis or viral hepatitis). Best objective response of target liver lesions was assessed using RECIST.
Using a modified 3 + 3 design, the planned sample size laid between two and 38 evaluable patients in case of two DLTs in the first two patients and two full cohorts at each dose level, respectively. For the primary endpoint, the following patients were considered evaluable: either patients who experienced a DLT and received a dose of at least 12Gy or patients who completed the treatment according to their dose level. Non-evaluable patients were to be replaced. Primary endpoint was DLT. Best objective response of target liver lesions and adverse events were assessed as secondary endpoints. Local control was defined as time from registration to progression of target lesions or death due to progression, whichever occurred first. Overall survival was the time from registration to death from any cause. The rates at one year of these survival times were estimated using the Kaplan-Meier estimator. Point estimates and, if applicable, the corresponding exact 95% confidence interval were calculated for proportions. Median follow-up time was calculated using the reverse Kaplan-Meier method. All data were collected and analyzed at the SAKK coordinating center in Bern, Switzerland. Analyses were performed using SAS 9.2.
The trial was terminated early due to low accrual. Therefore only dose levels 1–3 (54, 58 and 62Gy) were examined.
From November 2008 to January 2014, 19 patients from five centers within Switzerland and the Netherlands were recruited; six patients at dose level 1, seven patients at dose level 2 and six patients at dose level 3. One patient was not treated at all with RT because of inadequate normal liver volume < 800 ml and therefor not evaluable for both endpoints.
In DL 3, three additional patients were not evaluable for the primary endpoint: two died during treatment one due to cardiac failure and one due to pneumonia (at 26 and 30Gy in 2Gy per fraction, respectively), and one because laboratory values were repeatedly not measured, making it impossible to assess DLT. The remaining 15 patients completed RT as planned, and were evaluable for the primary endpoint. For the secondary endpoints, 18 patients (95%) were evaluable. Median follow up time was 11.8 months. The median age was 68 years (range 45–82 years, inter-quartile range 62–77). The majority of HCC patients had stage cT3 (47%), cN0 (84%) disease, CP-score A5 (58%) and WHO performance status 0 (53%). Alcohol was the most common etiology of the underlying liver cirrhosis (74%). Two patients (11%) had M1 disease. Median longest diameter of largest lesion was 68 mm (range 18–230 mm). Median administered RT dose was 57Gy (range 26–62Gy in 2Gy per fraction). Other baseline patient characteristics can be found in Table 1. Median longest diameter of largest lesion was 70 mm (range 18–185 mm). Median administered RT dose was 57Gy (range 26–62Gy in 2Gy per fraction).
At dose levels 1 and 2, six patients each and at dose levels 3, three patients were evaluable. One (17%) of 6 patients in dose level 1 and one (17%) of six patients in dose level 2 experienced DLTs (lipase > 5xULN and neutrophils <500/μL). Both, dose levels 1 and 2 had a DLT each among the first three patients, requiring an additional three patients at the same dose level as per protocol. However, dose level 3 (62Gy) was completed, with no DLTs in three patients. Two patients died during RT treatment, one patient in dose level 2 due to cardiac failure, and one in dose level 3 due to pneumonia. One patient in dose level 3 died during follow-up, due to cardiac failure. None of the deaths were related to RT treatment. None of the in total evaluated patients showed any signs of RILD. At dose level 1, one patient developed an elevated lipase value grade 4 (Lipase > 5 x ULN) during the first week of RT, which subsequently normalized on laboratory follow-up. A second patient showed an elevated grade 4 bilirubin value (Total bilirubin > 10 x ULN) one month after RT, which normalized, and a third patient showed an isolated elevated AST grade 4 (AST > 20 x ULN) three months after RT, which also normalized during the subsequent analyses. At dose level 2, one patient experienced neutropenia grade 4 (neutrophils <500/μL) in week 6 of RT and at dose level 3, two patients each experienced lymphocytopenia grade 4 (lymphocytes < 200/mm3) during week 5 and 6 as well as during week 6 and at the end of RT, with no clinical impact.
Response rate
The overall RECIST response rate was 56% (95% CI 31–78%), with 0% complete response (CR), 56% partial response (PR) and 28% stable disease (SD). In three patients (16%), treated at dose level 3, no response (NR) could be determined. Two patients died and one had symptomatic deterioration before their first CT scan after baseline. An overview of response rate according to DL and CP-Score are shown in Tables 2 and 3. The most frequent site of first progression was outside the treated volume. One-year survival and 1-year local control in this small cohort is 61% (95% CI: 35–79%) and 89% (95% CI 43–98%), respectively, which were not endpoints within the trial (Fig. 1).
We present the data of an international multicenter phase I study of 18 patients treated with cfRT for locally advanced non-resectable HCC. In contrast to previously published prospective studies [10, 15–18], DLT in the present trial was specifically defined for 17 clinical and nine laboratory parameters as grade ≥3 or ≥4 toxicity (CTCAE vs. 3), to address the safety aspect from a biochemical point of view. Additionally, our study-population had large tumors (median 86 mm, range 18–230 mm) and 20% of patients had a CP B score. Even in such a vulnerable patient collective, the present trial showed that cfRT of 58Gy to HCC is safe in an international multicenter setting. A total dose of 62Gy was delivered to three patients without any sign of clinical relevant increased toxicity. However, the maximum tolerated dose could not be determined due to the early termination of the trial because of patient accrual. The reasons for very slow patient accrual included several competing focal treatment options (e.g. RFA, TACE) in liver tumors and the rapid evolvement of SBRT. RT was well tolerated in this study, and no signs of RILD were observed. The DLTs at dose level 1 (54Gy) and 2 (58Gy) (lipase > 5xULN and neutrophils <500/μL) were not clinically relevant. The increased lipase value occurred in the first week of RT at DL 1 and was most likely not related to RT, since it normalized in the subsequent weeks of treatments, when higher cumulative doses were applied. The decreased granulocyte value may have corresponded to an increased granulocyte consumption, which may be interpreted as an expression of intermittent hepatocyte injury [19]. During follow-up, there was a spontaneous remission of the neutrophils in the physiological range. Therefore it is questionable to use the lipase and neutrophils as a dose-limiting factor for RT induced liver injury. The isolated bilirubin elevation one month after RT and isolated AST elevation at 3 months after RT were only present at dose level 1. No patient in dose level 2 and 3 had similar laboratory changes, even though higher doses were applied. The grade 4 adverse events were transient, and all patients recovered spontaneously within a few months. None of the two patient's deaths in this trial were related to RT treatment.
Several studies showed that it is safe to treat HCC patients with cfRT in HCC. In a series of prospective trials [10, 15–18], the University of Michigan group first established the safety of an individualized dose allocation approach for liver cancer. They developed a NTCP model that quantitatively described the relationship between dose and volumes irradiated and the probability of developing classic RILD using conformal RT techniques. Radiation dose was individualized based on the volume of normal liver that could be spared without exceeding a 5–20% risk of RILD. Objectively measurable disease was not an entry criterion, although it was followed when available. The prescribed doses ranged from 40–90Gy (median, 60.75Gy) in 1.5Gy twice-daily fractions delivered with concurrent hepatic arterial fluorodeoxyuridine [2]. In a phase II trial, Ben-Josef et al. [10] reported median survival of 15.8 months with a trend to improved survival (23.9 vs. 14.9 months) in patients treated with doses of ≥75Gy. Doses below 60Gy had little effect on survival and then a steady increase in survival was observed as RT dose increased to 90Gy. Of the 128 patients, 30% patient developed mostly biochemical grade 3 to 4 toxicity, five patients (4%) developed RILD. In a large retrospective series from Korea [20] including 158 HCC patients with CPS A or B were treated with 25–60Gy in 1.8Gy daily fractions. The patient selection was similar to the one of the present trial. Median overall survival time was 10 months, with no grade 4 or 5 toxicity reported. They demonstrated that the CP score was a significant factor in the development of RILD and the total radiation dose was the only significant factor determining the tumor response. The same group [21] reported in a retrospective patterns of care study of 398 patients, with HCC treated at 10 institutions in Korea, that CPS A, tumor size <5 cm, negative lymph nodes and BED > 53.1Gy (alpha/beta of 10) were significant factors for a better prognosis. In their collective BEDs between 4.2–124.3Gy were delivered, the median survival time was 12 months, and the 2-year overall survival rate was 27.9%.
For that reason we suggest, that dose escalation, exceeding 62Gy, should be chosen based on the NTCP of the surrounding liver tissue. One-year survival and 1-year local control in our trial with this vulnerable cohort were 61% and 89%, respectively, although they were not endpoints in the present study.
The overall RECIST response rate in our trial was 56%, with no patient showing a CR. Mornex et al. [22] showed in their phase II trial, including 27 patients, a 92% response rate using the WHO and RECIST 1.0 criteria. Ninety-six percent of patients received an RT dose of 66Gy. However, they only included patients with small-size HCC between ≥30 and ≤50 mm, whereas in our trial, tumor size ranged from 18–230 mm. Of all patients, 41% developed grade ≥3 toxicity: 19% asymptomatic grade 3 laboratory parameters toxicities in CPS A patients and 27% grade 4 laboratory parameters toxicities, 15% late grade 3 toxicity consisting of gastric bleeding requiring transfusion, and edematous-ascitic hepatic decompensation requiring paracentesis and diuretics in CPS B patients.
Liu et al. [23] treated 44 patients with large HCC (60–250 mm) with 40–60Gy in standard fractionation. Tumor response was based on serial CT scans, with an overall response rate of 61% using the WHO response rating criteria. Radiation-induced toxicities remained mild and reversible. Their results are comparable with the results of our study. Similarly, a retrospective study of Toya et al. [24] treated 38 HCC patients with PVTT and tumor sizes ranging from 9 to 93 mm. A total dose of 17.5–50.4Gy (median 40Gy), in 1.8–4Gy per fraction was delivered, which translated to a BED of 23.4–59.5Gy (median 50.7Gy) with an alpha/beta of 10. Response rate was 44.7%. In 13 patients treated with 45Gy in 3Gy per fraction, the response rate was 76.9%. The PVTT size (≤30 mm vs. ≥ 30 mm) and BED ≥58Gy (alpha/beta of 10) were factors, which significantly were influencing response rate and survival. The median- and one-year survival was 9.6 months and 39.4%, respectively.
However, using the RECIST criteria to evaluate RT response rate is outdated. It has been shown that extensive tumor necrosis after loco-regional ablative treatment or systemic chemotherapy may not always be followed by an overall reduction in tumor diameter. In some instances the lesion size may even increase due to necrosis [25]. Several recent studies [26–30] have demonstrated that quantification of residual viable tumor by the European Association for Study of the Liver (EASL) and modified RECIST (mRECIST) guidelines better predict treatment response compared with WHO and RECIST guidelines. Volumetric response assessment is likely to become the gold standard for defining treatment response [31, 32]. Our protocol was written during a period of time, when the mRECIST guidelines were not standard yet. The available literature on response rates after cfRT reports in WHO or RECIST criteria.
The presented data is well comparable with the existing data within the literature. However, it has its limitations. It is a small number of patients and the maximum tolerated dose could not be determined due to the early termination of the trial. Also the trial duration was long. During this time period other effective treatment techniques such as SBRT or proton beam therapy have evolved. SBRT refers to the use of stereotactic non-coplanar conformal radiation therapy to precisely deliver a large ablative radiation dose in a small number of fractions, while limiting the dose to adjacent normal tissues. The steep dose gradient within the target volume leads to tight conformity with steep and isotropic dose fall-off and high dose delivery to the target volume [33]. There is a growing SBRT experience, mostly in patients with small (<6 cm) HCC [34–38] with a high local control ranging from 70–90% at one and two years. In a large Canadian phase I/II study by Bujold et al. [39], 102 patients with locally advanced HCC (median size, 10 cm) were treated with six fractions of SBRT, with a 1-year local control rate of 87% and median OS of 17 months. Despite limiting their study to a CP A score population, CP class deterioration occurred in 29% at 3 months. Proton radiotherapy has also emerged as a treatment option for patients with localized HCC. It enables further dose escalation and precise dose delivery while maintaining a favorable toxicity profile. Various phase II trials have demonstrated the effectiveness and toxicity profile of this therapy [40–42].
Recent studies have compared SBRT and proton beam therapy to other focal treatment options such as RF or TACE [43–45] in early stage HCC patients. Wahl et al. [43] have published a retrospective study comparing SBRT to RF in inoperable patients with small HCC. For tumors treated with RFA, freedom from local progression (FFLP) at two years was 80.2% vs. 83.8% for SBRT. Increasing tumor size was predictive for FFLP in patients treated with RFA (hazard ratio [HR], 1.54 per cm; p = 0.006), but not for those treated with SBRT (HR, 1.21 per cm; p = 0.617). For tumors ≥2 cm, there was decreased FFLP for RFA compared with SBRT (HR, 3.35; p = 0.025). Takeda et al. [44] conducted a phase II study, treating 90 CP A and B score patients with a solitary HCC lesion up to a diameter of 4 cm, unsuitable for resection and RF with SBRT and optional TACE. Three-year LC rate and OS was 96.3% and 66.7% (95% CI, 56.3–75.6%) respectively. In an other phase II study Bush et al. [45] compared proton beam therapy to TACE as a bridge for transplantation. In an interim analysis of 69 subjects, ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (p = 0.38). The two-year OS for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% CI 20.7–39.3 months). There was a trend toward improved two-year LC (88% vs. 45%, p = 0.06) and progression-free survival (48% vs. 31%, p = 0.06) favoring the proton beam treatment group.
However, large, inoperable HCC > 10 cm, remain challenging for treatment, because of close proximity to critical organ, limited liver volume available and a relatively poor liver functional status. In this small niche of treatment indications, when locally ablative treatments like RFA, TACE or SBRT are not possible, cfRT remains a valid treatment approach for liver cancer [46]. Conventional fractionation schedules may be more robust for certain patients with large tumors or at risk for fibrosis of the biliary ducts. The relatively high alpha/beta ration of 8 [47] of liver tissue implies highly conformal therapy, if treatment is completed within a few sessions. Nevertheless, the use of SBRT is being preferred whenever feasible. The steep dose gradient within the target volume leads to tight conformity with steep and isotropic dose fall-off and high dose delivery to the target volume and requires, due to the complementary information, when ever available the addition of MRI imaging to GTV delineation as well as appropriate motion control [48].
Despite increasing utilization, and prospective phase II studies [39] describing favorable outcomes, SBRT for liver cancer is still not included in practice guidelines [49–51]. There is currently one randomized phase III trial by the RTOG (RTOG 1112, (ClinicalTrials.gov ID: NCT01730937) open for accrual, comparing Sorafenib versus SBRT followed by Sorafenib in locally advanced HCC. This trial hopefully will help to better clarify the role of RT in HCC.
This multicenter trial showed that conventionally fractionated radiotherapy delivering 58Gy to large primary tumors of the liver was safe for patients with CPS A and B. The dose of 62Gy was delivered to three patients without any sign of increased toxicity. However, the maximum tolerated dose could not be determined due to the early termination of the trial. Randomized trials are warranted to further define the role of cfRT and SBRT within multimodal treatment concepts for unresectable HCC.
3D-conformal RT
Biologically effective dose
- cfRT:
Conventionally fractionated radiotherapy
Child-Pugh score
Complete response
Computed tomography
- CTCAE vs. 3:
Common toxicity criteria for adverse events version 3.0
Clinical target volume
Dose-limiting toxicity
Dummy run
European Association for Study of the Liver
External dosimetry audit
Gross tumor volume
Hepatocellular carcinoma
Intensity-modulated radiotherapie
International normalized ratio
- mRECIST:
Modified RECIST
Maximum tolerated dose
No response
Normal tissue complication probability
Organs at risk
Partial response
Planning target volume
Portal vein thrombosis
Response evaluation criteria in solid tumors
Radiofrequency ablation
Radiation induced liver disease
Radiotherapy specific quality assurance
Swiss Group for Clinical Cancer Research
Stereotactitc body radiotherapy
Stable disease
Transarterial chemoembolization
Tolerance dose
Upper limit of normal
Volumetric arc therapy
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Not applicable.
Availability of data and materials
The datasets supporting the conclusions of this article are included within the article.
Authors' contributions
Each author had participated sufficiently in the work to take public responsibility for appropriate portions of the content. IFC, DN, JFD and DMA designed this Study. MB performed the statistical analysis. All authors helped to interpret the data. The manuscript was written by EH, MS and MB, all other authors helped and finally approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
The study was planned and conducted in accordance with the principles of the Declaration of Helsinki. The protocol was approved by the ethics committee of each participating site (ClinicalTrials.gov identifier NCT00777894, registered October 21st, 2008). Written informed consent was obtained from all patients.
Financial support
By the Carolito Fundation, Swiss Foundation for Clinical Cancer Research and the Swiss Federal Secretariat for Education, Research and Innovation.
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Cite this article
Herrmann, E., Naehrig, D., Sassowsky, M. et al. External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26. Radiat Oncol 12, 12 (2017). https://doi.org/10.1186/s13014-016-0745-0
- Hepatocellular carcinoma
- Conformal radiotherapy
- Liver
- Radiation toxicity


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As I mentioned earlier this month (click HERE for details), I made the decision to leave my Wednesday morning bible study. A decision not taken lightly, especially when it means I will no longer be leading this lovely group of women:
So I thought a little gathering was in order. And introducing them to 'my new thing' seemed the perfect way to do just that! The August IF:Table was comprised of ladies from my former small group.
Not only did we feast on Honey-Dijon Chicken, Recipe Girl's Three-Berry Salad with Sugared Almonds, Cheesy Pesto Garlic Bread, and Berry Slab Pie – we laughed until we cried, talked about the possibility of meeting over Jennie Allen's book Restless, shared stories, and simply enjoyed being in each other's company for two hours.
And I very much look forward to doing it again (perhaps even with a new face or two!) as we venture into the cooler months.


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September 2015
Dubai-headquartered Transguard Group in conjunction with US-based multinational company Sealed Air is currently trialing cleaning robots at Dubai Festival City Mall in what is considered as a first for the UAE and the wider region.
There are three different types of cleaning robots in the Sealed Air Diversey Care products range called Intellibots. Each machine is designed for a particular type of floor and environment. The robot on trial at Dubai Festival City Mall, is the Hands-Free Cleaning HydroBot Scrubber, which is specifically intended for hard floors and is ideal for retail environments, such as indoor shopping malls.
"The versatile HydroBot allows the operator to switch between manual cleaning and Hands-Free Cleaning, so at the push of a button the operator can walk away to clean in other areas," said Charlotte Butt, senior manager of mobilisation, Transguard
The Hands-Free Cleaning operating system incorporates up to 19 sensors, giving the robot a 360-degree view of its surroundings and allowing it to operate and clean on its own. Advanced navigation and sensors detect obstacles as well as people – stopping to let them pass before proceeding – and stairs, to prevent unwanted spills.
"Supervisors can also monitor progress at any stage and receive wireless 'end of shift' report, including the location of the robot, operator identity, running times and the specific areas cleaned," added Butt.
The HydroBot also comes equipped with Eco Save which is an advanced four-stage purification system that can filter water to one micron, providing clean, reusable water and eliminating up to 85 per cent of its wastewater and chemicals, which significantly lowers its impact on the environment.


text: Even if you wear a size small, you can still be carrying a bit of extra poundage in certain places. You know what we say, though? You are beautiful! And you can yoga. This women's t-shirt is made from 100% cotton (solid shades) or 90/10% cotton and polyester (heather shades). It features near-cap sleeves, a scoop neck and a flattering silhouette to showcase your curves. Comes in not-too-thick, a bit thick, thick, thicker, super-thick and thickest (or, if you prefer, S, M, L, XL, 2XL and 3XL). You don't need to hide your size - flaunt it with this great tee, and rock that yoga mat!


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As the sun peaks through, we don our work clothes and walk to the barn. Beneath my black boots the grass is wet from the rains that fell during the night. A chorus of birds breaks the silence and awakens me. The air smells of spring – the mix of freshly dampened dirt, compost and grass – inviting me to treasure the renewed life breaking forth all around me. Spring. It's been long-awaited this year. The desolation seemed to crawl into weeks of unwelcome. But, on this blessed morning they are but a memory.
In the Bible there's a little book that closes the Old Testament. By this time the Israelites had returned from exile and some hundred years had passed since the Babylonian Captivity had ended. Both Haggai and Zechariah had prophesied that the rebuilding of the temple would bring prosperity and peace, and the return of God's glorious presence. However, the temple work had been going on for about eighty years, and the Israelites found themselves in ruin. The desolation crawled into weeks of unwelcome hurling themselves into years of anguish. They had lost their independence and were no longer ruled by a Davidic King. Brokenness was all around them with droughts and failing crops. But all of this was insignificant compared to their ache for God's presence. Haggai and Zechariah's prophecies must have left an empty void in their hearts as they longed for the return of their God.
Malachi is a book that reveals just how far the Israelites' hearts had strayed. Six times Malachi raises issue with the way the Israelites are living. Six times Malachi confronts the people. And six times the desolation that is coming due to this poor behavior is announced. After bold assertions regarding unbelievers, a glimmer of hope is announced, and Malachi tells the people that there is a day coming when the wrong of the world will be made right.
"For behold, the day is coming, burning like an oven, when all the arrogant and all evildoers will be stubble. The day that is coming shall set them ablaze, says the Lord of hosts, so that it will leave them neither root nor branch." (Malachi 4:1)
Through the heaviness of the air, God breathes hope.:
"But for you who fear my name, the sun of righteousness shall rise with healing in its wings. You shall go out leaping like calves from the stall."
During the winter months here in Minnesota we keep our herd of cows close to the barn. On the coldest of nights, we lock them in the barn. As they huddle together their heat warms the space. As the days and weeks go by, their stalls beg to be cleaned. The hay that was fresh and green last summer loses its appeal and begins to smell of dust rather than the grassy aromas of summer. Reluctantly the cows munch the hay their appetites satiated with the tired grasses. Everything longs for the rebirth of the world.
One of my favorite moments in spring is when we open the pens of the cows. These huge animals gingerly step out of the fences that have held them in for months. They taste the fresh new grass. They take a few more steps. And, then they begin leaping! Even the bull with his sturdy frame and great girth enjoys the dance. Unencumbered – finally – the animals surge forward and a flood of joy covers the pasture as they taste the richness.
The Israelites were awaiting this day. For four hundred years, our God was silent. Then, quietly, softly, He stepped into our world in a whole new way. After 30 years of living a perfect life, He died the death of a thief, a murdered. But the story doesn't end there. He rose again and now is preparing a place for us. A place where just like the cows we will leap for joy. In this place the desolation that becomes weeks of unwelcome will end. No longer constricted by the aches and pains of this world. No longer stifled by the evil that is so present among us. No longer broken... God's creation will be rebirthed. This day is coming for us when unencumbered – finally – we will step into a new space and a flood of joy will cover that which is before us. And all that we are and all that we have will bow before the Lord and bring Him glory and honor and praise. And, oh! How we will leap for joy!


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Two more former major champions, Bubba Watson and Ernie Els, have confirmed they will take part in the World Golf Championships-HSBC Champions in China next month.
They join defending champion Martin Kaymer, Phil Mickelson, Keegan Bradley, Graeme McDowell, Louis Oosthuizen and a host of other star names in the field for the final WGC of the year.
The event will be staged from November 1-4 on the Olazabal Course at Mission Hills, located in China's Guangdong province.
Watson, the 2012 Masters champion, will be making his first start in the WGC-HSBC Champions, and is relishing the prospect of his first ever trip to China.
"Winning my first major at the Masters in April has made this an amazing year but I haven't won since, so I'd love to end my year with my first World Golf Championship win," said the left hander.
"Asian golf is definitely on the up and I am excited to go there, see it and experience it for myself."
Els, who won his second Open and fourth major championship at Royal Lytham and St Annes this summer, is also looking forward to the event.
"Winning my second Open at Lytham was obviously a very special moment in my career, and I guess you could say I've had a spring in my step ever since," he said.
"I'm definitely enjoying my golf and, as always, I'm excited about the prospect of returning to Mission Hills for the WGC-HSBC Champions. It's always a fantastic week."
World numbers three and four, Luke Donald and Lee Westwood, will also take part in the $7m event, staged for the first time at Mission Hills after seven editions at Shanghai's Sheshan International Golf Club.


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In December 2014, we posted an article about the inspiring individual Kennedy Jones to preview a program that he decided to begin in early 2015 as a New Year's resolution – #KJPAYDAY. This program is his way of giving back to his most dedicated fans. So without further ado, here is a guest editorial written by Kennedy about his #KJPAYDAY program and the recipient for the month of January.
Words by Kennedy Jones…
In December 2014 I announced that I would be paying one fan's bill, once a month for the year of 2015. This is called the #KJPAYDAY program. #KJPAYDAY enables me to directly give back to the #TeamKJ family. I will be picking a different fan every month for whom I will pay a bill of their choice. This is all done on a case by case basis but will be at random. I may pick a fan that I meet out at a show, someone that I see constantly supporting #TeamKJ on Twitter, Facebook, Instagram, and Soundcloud, as well as when I see someone who goes out of their way for someone else or constantly is radiating positivity. Some alternate ways to be considered for #KJPAYDAY will be announced on my Facebook/Twitter each month. This is all about YOU. I always want to find new ways to show my appreciation to my supporters. I want my music to touch lives in a positive way but also, I want to go beyond just the music. I want to show you all how #TeamKJ can come full circle and make incredible differences in people's lives that in turn, make incredible differences in the world. I understand that when the music shuts off after a show, life is in session. There is a life outside of the clubs, venues, and festivals that sometimes could be weighing heavier on our fellows than we even know. I understand that because I have lived it, I still live it everyday. This is a way to help some people that are just like you, just like us. This is a chance to be a part of something bigger than all of us. Your support for #TeamKJ thus far has made this program possible. While supporting the music scene as a whole, you have also already contributed to a program that will help others. I also do this because I know what it's like to sometimes need a break. WE ALL DO. Anyone that portrays invincibility is a fraud. I want to be able to offer a helping hand to those who need that break so they can reach their goals and hopefully help someone in the process.
Meet Katy Olsen, the selected #KJPAYDAY recipient of January 2015. After meeting Katy at a show in Dallas, Texas at the Lizard Lounge, she explained to me that her goal was to move to Thailand to teach English to children. Katy had no idea about the #KJPAYDAY program at this point; she was genuinely enthusiastic about this huge life decision and I could just hear in her voice how convicted she was of her cause. Katy graduated from the University of North Texas in 2014 with a degree in integrative studies with a focus in Psychology and Rehabilitation and has been working tirelessly for a finance company trying to make enough money to pay her student loan, among other bills, and to afford her one way plane ticket to Thailand. I reached out to Katy shortly after returning home and told her that I admired her goal and wanted to help her reach it. Her reaction was absolutely priceless. Nothing beats the sound of someone's voice when you can really help them through something that they've been working so hard for. After paying the January 2015 balance of Katy's monthly student loan bill, I received the following email from her:
"By you paying my student loan bill, I was able to free up a ton of extra money to buy my one way plane ticket to the other side of the world to teach English to children in Thailand. I couldn't thank you enough for helping me fulfill my dreams! I'll never forget the amazing friends and family I've met in this scene, especially you! <3 My favorite part about the #KJPAYDAY program is the fact that you are simply so humble. I randomly met you one night at Lizard Lounge and you had remembered meeting me 6 months prior in the middle of the crowd at Mad Decent Block Party. We talked for about half an hour and you were so down to earth and it reminded me of why I have been in these scene for 5+ years now. Our scene takes such a blow sometimes from the negative press but you reminded me of why we're all here in the first place. For the music and the love. You are truly a blessing! I'm going to remember this for the rest of my life and be sure to pay it forward as much as I can during my time in Asia.
-Katy Olsen"
Being able to help the people that support me is such a gift. It is an opportunity that I could never thank all of you enough for. The constant support and encouragement you all give me, and how strong of a movement #TeamKJ has become in the music world is incredible. This is all about creating music that will connect people whose paths would not usually cross. It's about being honest with ourselves, growing as individuals, and selflessly helping the next person through the love and spirit of music that binds us. It's about allowing music to heal us, having fun, and making lifelong relationships. It's about not letting the "show biz" of "show biz" blind us from seeing the true beauty that comes of the music and the PEOPLE that support it. I am happy to have such an incredible host of fans who are constantly spreading love and keeping it 100 out there in the world. I am proud to have each of you representing #TeamKJ and setting an example for years to come. I will always have my eye out looking for the next monthly recipient of #KJPAYDAY. As we launch into 2015, I will be releasing more music, playing more shows, and organizing #TeamKJ volunteering projects across the world so that I get to work with all of you in person making a difference in your community. This has been an incredible journey and as we continue to grow, I cannot tell you how grateful I am to be doing all of this with YOU at my side. I want the hashtag #KJPAYDAY to be used not just to represent this program, but to represent a movement that involves helping others. Use it freely and spread the word and vibes! I love all of you and cannot wait to see you on the road someday!
Best Wishes and Love,
Kennedy Jones
#KJPAYDAY Requirements of Recipient if Selected:
–Must provide a scanned copy of the bill you want paid.
-Amounts are reviewed on a case by case basis.
-Recipient must be 18 years of age or older (Or with written parent consent to participate).
-Selected participant may be asked to provide a photo and some personal information to be shared in the recap of their selection.
To contact Kennedy Jones #KJPAYDAY about this program, please send an email to [email protected]. Please understand that not all emails may get a response depending on volume, but they will be checked and read. For Management/Press inquiries, please contact [email protected]


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|Click the image for a closeup!
So here you go. Find a big cork and set it on the table, wide end down. Saw through the center of the narrow end, back and forth, using a sharp knife or craft blade (Kids, ask a parent. Knives are sharp). Squeeze the sides together to stabilize the cork and saw gently. Cut a slit about halfway down the cork.


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Small Business Saturday helps local merchants
Last updated 11/21/2017 at Noon
Photo: Allissa Blackwell, left, and Jade Johnson look at the new Brighton jewelry Christmas pieces at the Classy Peacock in Bridge City Tuesday. The store is one of many in the area taking part in Small Business Saturday this weekend.
Black Thursday and Cyber Monday are set to send trucks load of Christmas cash flying out of Southeast Texas bank accounts to giant corporations.
Small Business Saturday helps the little guys, the epitome of the Shop Local movement.
The event was created by credit card company American Express in 2010, after the Wall Street crash of 2008-09.
It has turned into a boon for local merchants.
The program itself has become more prominent over the years too. Since 2011, Congress has designated a National Small Business Saturday, which is Nov. 25 this year.
Since its founding, it's been a powerful opportunity to reconnect with customers -- and boost sales.
Last year, 112 million shoppers participated spending more than $15 billion.


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Cranberry Apple Pie
Featured In
Total TimePrep: 15 min. Bake: 1 hour
Makes8 servings
- 2 cups sugar
- 1/4 cup cornstarch
- 1/4 cup orange juice
- 1/2 teaspoon ground cinnamon
- 1/2 teaspoon apple pie spice
- 1/8 teaspoon ground nutmeg
- 1/4 teaspoon lemon juice
- 4 cups sliced peeled tart apples
- 2 cups fresh or frozen cranberries
- Pastry for double-crust pie
- 2 tablespoons butter
- In a large bowl, combine the first 7 ingredients. Add apples and cranberries; toss gently. Line a 9-in. pie plate with bottom pastry. Add filling; dot with butter.
- Roll the remaining pastry to fit top of pie. Cut vents in pastry, using a small apple cutter if desired. Place over filling; seal and flute the edges.
- Bake at 425° for 10 minutes. Reduce heat to 350°; bake 50 minutes longer or until crust is golden brown and filling is bubbly.
Test Kitchen Tips
Nutrition Facts1 piece: 521 calories, 17g fat (8g saturated fat), 18mg cholesterol, 230mg sodium, 92g carbohydrate (60g sugars, 2g fiber), 2g protein.
Nov 17, 2018
Just made this pie and it is scrumptious! I even forgot the butter, but it still is my new favorite pie! Granny Smith apples and fresh cranberries make an unbeatable combination, just a little tart, yummy!
Nov 23, 2017
Flavor was great, but mine didn't set either as others have stated. I followed the directions exactly. I used braeburn apple and don't know if the type of apple make a difference or not. The flavor is good so I might give it another try with a different type of apple.
Dec 24, 2016
No comment left
Oct 5, 2015
Loved it!!! Perfect combination of sweet and tart.... will be making this regularly... thanks for sharing!
Jan 17, 2015
Will make this pie again and again. Was loved my all. Thank you so much.
Nov 8, 2013
We loved this pie! It didn't set up for me, so next time I will add more cornstarch, but the flavor was so good that it still gets five stars! I'll certainly be making it again - probably on Thanksgiving!
Feb 22, 2012
I would make this recipe again, again and again. Made it with no changes at all. My boyfriend and mom loved it. Used 50% sugar and 50% Slenda to lower sugars.
Nov 29, 2011
The perfect combo of sweet and tart! We loved this pie!
Nov 6, 2011
Super easy! I followed the instructions exactly, no variation and was surprised at not only how easy this pie was to make, but how incredibly wonderful it tasted! HUGE hit with my hubby! Definitely will be making again!!
Oct 18, 2011
Loved the flavor of this pie- however mine didn't set up so I guess next time I will add more cornstarch. It was very runny, but so delicious I will make it again!!


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Recently we were invited by 20th Century Fox to attend a fun press event for WALKING WITH DINOSAURS at FAO SCHWARZ!
Note: I was invited as media to this event and received a gift bag. Views expressed are always 100% my own.
We've been watching the video promotions for the "Walking with Dinosaurs" for weeks now and we were excited to join in craft activities that tied into the movie.
During the event my son enjoyed Dinosaurs cookie decorating (and eating!) while watching preview clips of the movie.
Then he had his face painted like one of the Pachyrhinosaurus and tried his best to scare me. I suggested maybe he shouldn't smile if he's trying to be a scary Dinosaur. LOL
We tried having him make a scary face again during our next photo opp, but again my son ended up being cute instead of scary. I couldnt help but smile and give him an "A" for effort.
We ended the event by looking at some of the upcoming "Walking with Dinosaurs" toys available at FAO Schwarz. There's lots for little Dino fans to choose from for a holiday gift idea.
After such a fun filled day, we're really looking forward to seeing "Walking with Dinosaurs" film when it released in theaters on December 20th, 2013
For the first time in movie history, audiences will truly see and feel what it was like when dinosaurs ruled the Earth. WALKING WITH DINOSAURS is the ultimate immersive, big screen adventure for families. Meet dinosaurs more real than you've ever seen as you take off on a thrilling prehistoric adventure, where Patchi, an underdog dinosaur, triumphs against all odds to become a hero for the ages.
Learn more about Walking with Dinosaurs - www.walkingwithdinosaurs.com/movie/
Also follow on Facebook - www.facebook.com/WalkingWithDinosaurs
And on Twitter - www.twitter.com/walkwithdinos


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Sorry about the annoying songs for titles thing… I love christmas music! Anyway, here is my Cropped Watercolor Santa lesson.
I love doing this lesson (with 3rd graders) because it forces them to draw and think in a different way than they are used to drawing. Zooming in on something doesn't seem to be a natural tendency for most and they sometimes have a hard time wrapping their heads around this concept. I tell them to really focus on the face and don't forget about important details like, "NO BUG EYES!" and "Santa is an old man so give him bushy old man eyebrows!"
It's also a great watercolor technique lesson because we mix colors for the skin and I have started telling them that Santa shouldn't look like he just overdid it in the spray tan booth. (hehe!) We also discuss how important it is to use just the right amount of water and color so that you can control where the paint goes. These always showcase different drawing styles and I love it.


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AR News, Sept. 16
Drew Fraser, a law professor at Australia's Macquarie University, was suspended from his job earlier this year for publishing a letter in an Australian newspaper that said immigration risked turning the country into a colony of the Third World. Now Dr. Fraser faces a new attack. After the Deakin Law Review accepted an article he wrote defending the White Australia policy, a lawyer for Australia's Sudanese community threatened to sue Deakin University for racial vilification if the journal published the article. Prof. Sally Walker, the Vice-Chancellor of Deakin University, has asked the journal to submit copies of the article to the university lawyer so he can consider the matter. Please write Prof. Walker at email@example.com to urge her to not to block publication of the article. As always, please be judicious in your choice of language. Inflammatory and insulting e-mails do more harm than good. If you do not wish to compose your own message, you may use the recommended text below.
Example text:
Dear Professor Walker,
I have learned from press reports that the Deakin Law Review has accepted an article from Prof. Drew Fraser of Macquarie University that some will find controversial. I understand there is pressure on your university to stop publication of the article.
I hope you will resist this pressure. Prof. Fraser's ideas should stand or fall on their own merits. It would be a serious defeat for free speech if Prof. Fraser is silenced simply because some people do not want to hear what he has to say.
Dissent, even if it gives offence, is one of the hallmarks of a free, democratic society, and I urge you to hold fast against those who would take away this freedom.
Sincerely yours,
(Posted on September 16, 2005)
The contents of this reconstructed website archive are copyright © 1990-2020 New Century Foundation. All Rights Reserved.


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- Cousins Who Geek
Captain Marvel: Higher! Further! Faster!
As I left the theater after seeing Captain Marvel my first thought was OMG THAT MOVIE WAS AWESOME! My second thought was how in the world do I write a review that contains no spoilers but still drives home how much I love this movie?
Easy…I'm not gonna write a review. Instead I'm gonna write about my key take aways that really stuck with me.
WARNING: I'm going to try my best to be as spoiler free as possible but stop reading NOW if you don't want to know anything! Just come back and read this once you've seen it.
Okay…good…here we go. The opening title is gonna hit you right in the feels. And yes I'm talking about the opening Marvel logo. It's an important tribute, so bring tissues.
This is the first female-lead Marvel movie. I think it's important that the Marvel team didn't go with one of their already established characters i.e. Black Widow, but instead choose someone new. Along those same lines the fact that this movie basically serves as a prequel for the modern MCU universe is pretty important (post-Captain America/pre-Iron Man era)
Remember when in Iron Man, Coulson says "this isn't my first rodeo" while now we know what rodeo he was talking about.
The soundtrack is a 90's girls dream. My middle and high school years were in the 90's so I can tie every single song in the movie back to a moment in my life. Like when I first heard No Doubt's "Just A Girl", Nirvana's "Come As You Are" or "I'm Only Happy WhenIt Rains" from Garbage.
Goose is now my favorite cat ever and I am not a cat person.
Finally, the overall message here is what stuck with me. There is a line that Carol Danvers delivers "I don't have to prove anything to you" that just screamed GIRL POWER. And that is exactly what this movie is about, girl power. I'm not talking about this in the meta sense (because she does kick a lot of butt). I'm talking about how women are told to hold our emotions back, how we are not good enough, we will not fly the planes, drive the cars, or just lead.
Carol Danvers breaks down every one of those blocks and proves that she is the most important piece of the MCU puzzle. There is a reason Disney/Marvel released this movie on International Women's Day.
So there you go, my kinda non-spoiler thoughts on this amazing film that puts the HER back into Hero and proves we can go Higher! Further! Faster!
#2019disneymovies #mcu #captainmarvel #marvelcinematicuniverse #CarolDanvers #marvel


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Plastic & Reconstructive Surgery Associates
2581 Samaritan Drive #102
San Jose, CA 95124
(408) 356-4241
Surgeon: Vincent D. Lepore, MD
This woman, in her 40s, wished to 'update' the Breast Augmentation she had over 15 years ago. She was very pleased with her breast aug, but has noted some slight sagging occurring naturally over time. She came to Dr. Lepore to discuss options, and decided on Breast Lift, and Breast Augmentation with Removal and Replacement of her original implants.
During surgery in our AAASF-accredited surgical facility, her original (390cc) Saline Implants were removed, and replaced with Extra High Profile Silicone Implants (650cc). Her Breast Lift, a Donut Mastopexy, was performed with incisions around the areola, a procedure providing a more moderate lift.Our patient is picture in the After photos, 7 weeks post-surgery. She is very happy with her results.


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Life's Too Short - Helen RollasonHodder & Stoughton, 2000, Hardback in Dust Wrapper.
Condition: Very Good+ - in Very Good+ DJ. Slightly lean otherwise a very well presented copy.
Illustrated with colour photographs. This is the moving and inspirational story of the TV presenter who captured the hearts of the nation with her courageous fight against cancer. In August 1997 Helen Rollason was diagnosed with advanced colon and liver cancer and was given three months to live. She defied the prognosis and over the next two years pressed on with her work and life, managing the rigours of treatment, notching up new achievements and constantly setting herself targets for the future. She finally lost her battle with the disease in August 1999.
Size: 9½" x 6¼". 240 pages.


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Swagbucks is a search engine (like Google, Yahoo, etc) that radomly awards you "Swagbucks" for searching the internet. Just download the FREE toolbar and start earning! Use the Swagbucks toolbar every time you search the internet. The more you search, the more you win. (You get 30 swag bucks just for signing up!) Then after you have accumulated some Swagbucks, cash them in for prizes. They post to your account and are available for use immediately.* You can get anything at the Swag Store HERE. The best deal is a $5 Amazon Gift Card for only 450 Swagbucks. You can accumulate as many gift cards as you like and then use them all at once to "buy" something totally free. I'm saving mine to do some Christmas shopping. Totally effortless--other than deciding what to buy!
Fridays are Mega Swagbucks Friday!
What does that mean?
Higher odds of winning big bills (100, 200, 500, 1000)....
making free FREE-er : )
making free FREE-er : )
Don't forget, you can also print grocery coupons and earn Swagbucks for using them too!
*Swagbucks can be redeemed immediately.
You may purchase 2 "like" gift cards per day.
You may purchase 5 "like" gift cards per month.
If you are planning to cash them in towards a major purchase (i.e. Christmas shopping) at the end of the year, I suggest cashing them in as you earn them. If you cash them in over time (for $5 Amazon.com gift cards, for example) you will get a bigger bang for your buck. If you are limited on time, you may cash them in for a higher dollar gift card, but it will cost you more Swagbucks.
Here's an example:
If you buy one $25 Amazon.com gift card, it will cost you 3150 Swagbucks. (price as of 1/10/11)
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With your remaining 900 Swagbucks that you saved, you could actually buy two more $5 Amazon.com gift cards. 3150 Swagbucks cashed in over time, are actually worth $35 in Amazon.com gift cards, instead of $25.


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Kern Tec is a processor of stone fruit seeds based in Austria. The largely undiscovered resources are carefully separated into seeds and shells in order to develop their maximum potential. Our company philosophy of 100% resource recycling is pursued through continuous innovation. Our sustainable products not only delight the environment, but above all our customers, who can rely on high-quality products.
There is great potential in stone fruit stones, whether apricot, peach, plum or cherry. They contain seeds, which contain many proteins and healthy oils. They are ideal for producing sustainable and high-quality products such as edible oils, snack products and natural cosmetics.
We only use carefully selected raw materials from Austrian and European fruit growers and processing companies, and with our energy-autonomous production we can create local products for the first time and thus provide meaningful added value from which everyone along the value chain benefits:
Additional source of income for farmers & fruit processors
Saving resources in the sense of circular economy
Sustainable and novel ingredients
since June 2019
compared to almond producers
partly funded by PreSeed (AWS) of BMDW and BMVIT


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Rochester, N.Y. – Semrock, Inc., today announced that the U.S. Patent and Trademark Office (USPTO) has awarded them registered trademarks for their highly acclaimed and award-winning BrightLine series of optical fluorescence filters, the ultra-sharp RazorEdge series of high-performance Raman optical
filters, and the StopLine series of deep single- and mult-notch filters.
As the BrightLine name so vividly portrays, these filters offer the highest peak transmission and superior contrast for maximum brightness. RazorEdge Raman filters provide the steepest edges to measure even the smallest Raman shifts and with deep laser-line blocking for maximum laser rejection. StopLine notch filters – a versatile complement to the RazorEdge filter – are the narrowest bandwidth thin film notch filters (as low as 9 nm) on the market, and are ideal for a variety of fluorescence and Raman instrumentation.
"The BrightLine, RazorEdge and StopLine names are becoming synonymous around the world for performance and reliability, and this official registration will help to ensure that these names are always associated with Semrock," said Dr. Victor Mizrahi, President & CEO of Semrock.
The BrightLine, RazorEdge, and StopLine names join the MaxMirror® ultrabroadband laser mirror, and the name Semrock itself, in being successfully registered by Semrock with the USPTO.
About Semrock:
Semrock manufactures high-performance optical filters that set the standard in optical filters for the biotech and analytical instrumentation markets. Semrock products include the highly acclaimed BrightLine series of fluorescence filters for microscopy, flow cytometry and other fluorescence-based instrumentation, exceptional filters for Raman spectroscopy, and unique biomedical laser system optics. Semrock's innovative products are made possible by combining modern ion-beam sputtering with Semrock's proprietary technology. Founded in September 2000, Semrock is based in Rochester, New York, a well-known center of optics, and has sales offices throughout the United States.
For additional information about Semrock, its innovative products, and its team of international distributors, visit the company website at www.semrock.com.
Amanda Valek-MacDonald
Semrock, a Unit of IDEX Corporation


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Kingsman: The Golden Circle director Matthew Vaughn, has shed light on how the Glastonbury sex scene was filmed in the movie, as this has been a controversial mystery to many. He said:
Well, that's the beauty of filmmaking, isn't it? We had to get a lens made, we had to get a camera position dollying very close to someone's body, but you didn't want to hurt them by mistake. Having to use Eggsy and then another hand, because it got quite intimate, as you'd say, and making that seamless. It was one of those things that could have been a disaster. In some people's minds I know that they think it's a disaster already because they didn't like it, which is fine and I respect it, but other people do like it.
Taron Egerton revealed also how he was not comfortable while filming the sex scene, too In an interview with Screen Rant. He said that Delevingne's husband "saved the world" as the hand we see in the movie scene was entirely the husband's, not his.
Source: Vulture


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Welcome to my last project log,
As mentioned in my previous post, the only thing that is pulling me back from my progress is the card calculation. I re-calculated the cards after my first play test 2 weeks ago, because the eel cards were overflowing the deck. But, during my second play test last week, I just found out that the block cards were overflowing the deck as well.
I fixed the calculation and did another play test session with my housemates this time (with the new calculation), and it was perfect.
Here's the new calculation:
- Eels : 17
- Escalators: 24
- Reverse: 12
- Block: 9
Total: 62 Cards
Note that I add an additional (1) card for Escalator and Reverse to balance the deck. This formula worked out pretty well during my 3rd play test session. It wasn't easy to balance the "card system" because I had to play…
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