External beam radiation therapy for locally advanced and metastatic gastrointestinal stromal tumors

BACKGROUND: The role of radiation therapy (RT) in the management of gastrointestinal stromal tumors (GIST) is not well described. Here we report our institutional experience for patients with locally advanced or metastatic GIST treated with RT. METHODS: Between 1997 and 2012, 15 patients with 22 GISTs were treated with RT at our center. The median age was 68 (range, 41–86). Fourteen patients had stage IV disease and 1 patient had stage IIIB disease, per the American Joint Committee on Cancer (AJCC), 7th Edition staging. Tumors were in a variety of locations, and were most commonly referred for palliative treatment. Eighteen of 22 tumors were symptomatic. Prior to RT, 14 of 15 patients received systemic therapy in the form of tyrosine kinase inhibitors (TKIs) (n = 11), chemotherapy (n = 4), or both (n = 1). TKIs were used concurrently for nine tumors (40.9%). No tumors were treated with concurrent chemotherapy. Several fractionation schemes were used, most commonly 3 Gy × 10 (n = 8). Local progression-free survival and overall survival were estimated using the Kaplan-Meier method. Acute toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: The median follow-up was 5.1 months (range, 1.3-28.3). At the time of analysis, 12 patients have died (80%). The estimated 6-month local progression-free survival and overall survival were 57.0% and 57.8%, respectively. Among the 18 symptomatic tumors, at least partial palliation was achieved in 17 (94.4%), and symptoms were completely palliated in eight (44.4%). Treatment was well tolerated, with no Grade 4 or 5 toxicities. There was no Grade ≥3 toxicity associated with concurrent TKI use. CONCLUSIONS: In this largest series to date of GISTs treated with RT, a high rate of palliation was achieved for symptomatic tumors in a cohort of advanced stage, heavily pretreated patients. Treatment was well tolerated, and concurrent use of tyrosine kinase inhibitor therapy was not associated with additional toxicity. While follow-up was short, durable control is possible for some patients, providing evidence that GIST is not universally radioresistant and that RT can provide an important benefit in patients with progressive or metastatic disease

Prevalence of patientreported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

Purpose Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. Materials and methods Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45–56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS C 3 and CTCAE C 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen’s kappa coefficient. Results Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of C3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score C3) improved during treatment (13.4% at week 5). ‘‘Poor’’ agreement was observed between patient- and clinician-reported proctitis (Cohen’s k = 0.11; n = 58); however, there was ‘‘good’’ agreement for diarrhea (Cohen’s k = 0.68; n = 58). Conclusions Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4–5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments

Early results of quality of life for curatively treated rectal cancers in Chinese patients with EORTC QLQ-CR29

<p>Abstract</p> <p>Purpose</p> <p>To assess the quality of life in curatively treated patients with rectal cancer in a prospectively collected cohort.</p> <p>Methods</p> <p>Patients with stage I-III rectal cancer who were treated curatively in a single institution were accrued prospectively. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29). Quality of life among different treatment modalities and between stoma and nonstoma patients was evaluated in all patients.</p> <p>Results</p> <p>A total of 154 patients were assessed. The median time of completion for the questionnaires was 10 months after all the treatments. For patients with different treatment modalities, faecal incontinence and diarrhea were significantly higher in radiation group (p = 0.002 and p = 0.001, respectively), and no difference in male or female sexual function was found between radiation group and non-radiation group. For stoma and nonstoma patients, the QLQ-CR29 module found the symptoms of Defaecation and Embarrassment with Bowel Movement were more prominent in stoma patients, while no difference was detected in scales QLQ-C30 module.</p> <p>Conclusions</p> <p>Our study provided additional information in evaluating QoL of Chinese rectal cancer patients with currently widely used QoL questionnaires. As a supplement to the QLQ-C30, EORTC QLQ-CR29 is a useful questionnaire in evaluating curatively treated patients with rectal cancer. Bowel dysfunction (diarrhea and faecal incontinence) was still the major problem compromising QoL in patients with either pre- or postoperative chemoradiotherapy.</p

Predictive Value of Initial PET-SUVmax in Patients with Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma

Introduction:We have previously shown that in early clinical stage esophageal adenocarcinoma, a positron emission tomography standardized uptake values (PET SUVmax) of <4.5 is associated with earlier pathologic stage and predicts better survival. In this study, we analyze the impact of the pretreatment PET SUVmax in patients with locally advanced esophageal adenocarcinoma who undergo preoperative chemoradiotherapy.Methods:We performed a retrospective analysis, selecting patients with adenocarcinoma of the esophagus who had a pretreatment PET scan and who received chemoradiotherapy before esophagectomy. Data recorded included demographics, PET SUVmax, treatment details, pathologic details, and survival data. Comparison of categorical variables was done by χ2 analysis, continuous variables by t test, survival analysis by the Kaplan-Meier method, and comparisons of survival using the log-rank test.Results:Between January 1996 and September 2007, 189 patients were appropriate for this analysis. The initial PET SUVmax was <4.5 in 28 patients and ≥4.5 in 161 patients. The two groups were similar with regards to demographics and treatment details. Patients in the low SUV group were less likely to show evidence of treatment response after chemoradiotherapy, including a higher likelihood of residual nodal disease and a lower likelihood of a pathologic complete response and estimated treatment response. However, both groups had similar survival.Conclusions:Although the initial PET SUVmax does not predict survival in patients with locally advanced esophageal adenocarcinoma who receive preoperative chemoradiotherapy, patients with a high initial SUVmax respond better to preoperative therapy. These results can be used to better select esophageal cancer patients for combined modality treatment

Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals – 2012

AbstractEarly in 2013, the World Health Organization (WHO) released a 2012 update to the 2002 State of the Science of Endocrine Disrupting Chemicals. Several significant concerns have been identified that raise questions about conclusions reached in this report regarding endocrine disruption. First, the report is not a state-of-the-science review and does not follow the 2002 WHO recommended weight-of-evidence approach. Second, endocrine disruption is often presumed to occur based on exposure or a potential mechanism despite a lack of evidence to show that chemicals are causally established as endocrine disruptors. Additionally, causation is often inferred by the presentation of a series of unrelated facts, which collectively do not demonstrate causation. Third, trends in disease incidence or prevalence are discussed without regard to known causes or risk factors; endocrine disruption is implicated as the reason for such trends in the absence of evidence. Fourth, dose and potency are ignored for most chemicals discussed. Finally, controversial topics (i.e., low dose effects, non-monotonic dose response) are presented in a one-sided manner and these topics are important to understanding endocrine disruption. Overall, the 2012 report does not provide a balanced perspective, nor does it accurately reflect the state of the science on endocrine disruption

Multicentre results of stereotactic body radiotherapy for secondary liver tumours

AbstractBackgroundSurgical resection is the standard treatment for liver metastases, although for the majority of patients this is not possible. Stereotactic body radiotherapy (SBRT) is an alternative local-regional therapy. The purpose of this study was to evaluate the results of SBRT for secondary liver tumours from a combined multicentre database.MethodsVariables from patients treated with SBRT from four Academic Medical Centres were entered into a common database. Local tumour control and 1-year survival rates were calculated.ResultsIn total, 153 patients (91 women) 59±8.4 years old with 363 metastatic liver lesions were treated with SBRT. The underlying primary tumour arose from gastrointestinal (GI), retroperitoneal and from extra-abdominal primaries in 56%, 8% and 36% of patients, respectively. Metastases, with a gross tumour volume (GTV) of 138.5±126.8cm3, were treated with a total radiation dose of 37.5±8.2Gy in 5±3 fractions. The 1-year overall survival was 51% with an overall local control rate of 62% at a mean follow-up of 25.2±5.9 months. A complete tumour response was observed in 32% of patients. Grade 3–5 adverse events were noted in 3% of patients.ConclusionSecondary liver tumours treated with SBRT had a high rate of local control with a low incidence of adverse events

Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally-advanced, unresectable non-small cell lung cancer (NSCLC)

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT

Facilitative parenting and children's social, emotional and behavioural adjustment

Facilitative parenting (FP) supports the development of children’s social and emotional competence and effective peer relationships. Previous research has shown that FP discriminates between children bullied by peers from children who are not bullied, according to reports of teachers. This study investigates the association between FP and children’s social, emotional and behavioral problems, over and above the association with dysfunctional parenting (DP). 215 parents of children aged 5–11 years completed questionnaires about parenting and child behavior, and children and teachers completed measures of child bullying victimization. As predicted, FP accounted for variance in teacher reports of children’s bullying victimization as well as parent reports of children’s social and emotional problems and prosocial behavior better than that accounted for by DP. However for children’s reports of peer victimization the whole-scale DP was a better predictor than FP. Contrary to predictions, FP accounted for variance in conduct problems and hyperactivity better than DP. When analyses were replicated substituting subscales of dysfunctional and FP, a sub-set of FP subscales including Warmth, Supports Friendships, Not Conflicting, Child Communicates and Coaches were correlated with low levels of problems on a broad range of children’s adjustment problems. Parent–child conflict accounted for unique variance in children’s peer victimization (teacher report), peer problems, depression, emotional problems, conduct problems and hyperactivity. The potential relevance of FP as a protective factor for children against a wide range of adjustment problems is discussed