Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer.

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.

Symptom clusters in patients with cancer with metastatic bone pain.

PURPOSE: The primary objective was to explore how patients' worst pain clustered together with functional interference items. Secondary objectives were to determine whether symptom clusters change with palliative radiotherapy (RT) and to compare the difference between responders and nonresponders to radiation. MATERIALS/METHODS: Worst pain at the site of treatment and functional interference scores were assessed using the Brief Pain Inventory (BPI). Patients provided their scores at baseline, 4, 8, and 12 weeks post-RT. A principal component analysis was performed on the 8 items (worst pain and 7 functional interference items) at all time points to determine interrelationships between symptoms. Principal components with an eigenvalue higher than 0.90 and explaining more than 10% of the variance were selected. The Cronbach alpha statistic was used to estimate the internal consistency and reliability of the derived clusters at baseline and at subsequent follow-ups. Robust relationship and correlation among symptoms were displayed with a biplot graphic. RESULTS: From May 2003 to January 2007, 348 patients with bone metastases that were referred for palliative RT were accrued into the study. There were 206 males (59%) and 142 females (41%), with a median age of 68 years (range, 30-91). Lung (26%), breast (25%) and prostate (24%) were the most common primary cancer sites. Treatment ranged from single to multiple fractions, with the majority of patients receiving a single 8 Gy (58%) and 20 Gy/5 (35%). The most prevalent sites of RT were spine (31%), pelvis (16%), and hips (15%). Two symptom clusters were identified. Cluster 1 included walking ability, general activity, normal work, enjoyment of life and worst pain. Cluster 2 included relations with others, mood and sleep. The two clusters at baseline accounted for 67% of the total variance with a Cronbach alpha of 0.87 and 0.70, respectively. In responders to radiation treatment, the two symptom clusters disintegrated at 4, 8, and 12 weeks post-RT. All symptom severity items improved over time (p < 0.0001). In nonresponders, two clusters had disappeared at week 4, reemerged at week 8, and disintegrated at week 12. CONCLUSION: Symptom clustering has proved to be therapeutically important because treatment of one symptom may affect others within the same cluster. The significant correlations between worst pain and the functional interference items reaffirm the importance of pain reduction as a treatment goal for palliative radiotherapy. By treating a patient's symptom of worst pain, it would subsequently ease their response burden on their daily functional activities by decreasing symptom severity, increasing function, and improving overall quality of life.

Possession of ATM sequence variants as predictor for late normal tissue responses in breast cancer patients treated with radiotherapy.

PURPOSE: The ATM gene product is a central component of cell cycle regulation and genomic surveillance. We hypothesized that DNA sequence alterations in ATM predict for adverse effects after external beam radiotherapy for early breast cancer. METHODS AND MATERIALS: A total of 131 patients with a minimum of 2 years follow-up who had undergone breast-conserving surgery and adjuvant radiotherapy were screened for sequence alterations in ATM using DNA from blood lymphocytes. Genetic variants were identified using denaturing high performance liquid chromatography. The Radiation Therapy Oncology Group late morbidity scoring schemes for skin and subcutaneous tissues were applied to quantify the radiation-induced effects. RESULTS: Of the 131 patients, 51 possessed ATM sequence alterations located within exons or in short intron regions flanking each exon that encompass putative splice site regions. Of these 51 patients, 21 (41%) exhibited a minimum of a Grade 2 late radiation response. In contrast, of the 80 patients without an ATM sequence variation, only 18 (23%) had radiation-induced adverse responses, for an odds ratio of 2.4 (95% confidence interval, 1.1-5.2). Fifteen patients were heterozygous for the G-->A polymorphism at nucleotide 5557, which causes substitution of asparagine for aspartic acid at position 1853 of the ATM protein. Of these 15 patients, 8 (53%) exhibited a Grade 2-4 late response compared with 31 (27%) of the 116 patients without this alteration, for an odds ratio of 3.1 (95% confidence interval, 1.1-9.4). CONCLUSION: Sequence variants located in the ATM gene, in particular the 5557 G-->A polymorphism, may predict for late adverse radiation responses in breast cancer patients.

The Concise Guide to PHARMACOLOGY 2015/16: Overview.

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

Convalescence care for seniors of lower Manhattan: an interdisciplinary outreach, rehabilitation, and education model.

The purpose of this study was to test the efficacy of an interdisciplinary geriatric outreach, rehabilitation, and education program for seniors. Community-dwelling Chinese seniors in lower Manhattan were recruited through outreach activities (17 educational workshops, three community health fairs, media interviews) and community physician referrals to offer rehabilitation services. The instrument administered at entry and exit included questions about pain intensity, quality of life, activities of daily living (ADLs), and an assessment of a variety of intrinsic and extrinsic barriers to life participation. The sample included 70 seniors (53 women) with a mean age of 70.5 +/- 7.48 years (range 60-93 years old) of whom 86% were Cantonese-speaking Chinese. The barriers-to-life participation assessment revealed cultural, communication, transportation, and physical environmental barriers as well as insufficient financial resources. Thirty-four patients who completed the program showed a significant improvement in quality of life. Patients' reports reflected a high degree of satisfaction with the program. Interdisciplinary team-oriented patient care, including a physiatrist, social worker, and rehabilitation staff, may result in good outcomes and high patient satisfaction in ambulatory community seniors.

Isolated unilateral rupture of the alar ligament.

Only 6 cases of isolated unilateral rupture of the alar ligament have been previously reported. The authors report a new case and review the literature, morbid anatomy, and pathogenesis of this rare injury. The patient in their case, a 9-year-old girl, fell head first from a height of 5 feet off the ground. She presented with neck pain, a leftward head tilt, and severe limitation of right rotation, extension, and right lateral flexion of the neck. Plain radiographs and CT revealed no fracture but a shift of the dens toward the right lateral mass of C-1. Magnetic resonance imaging of the cervical spine showed signal hyperintensity within the left dens-atlas space on both T1- and T2-weighted sequences and interruption of the expected dark signal representing the left alar ligament, suggestive of its rupture. After 12 weeks of immobilization in a Guilford brace, MRI showed lessened dens deviation, and the patient attained full and painless neck motion. Including the patient in this case, the 7 patients with this injury were between 5 and 21 years old, sustained the injury in traffic accidents or falls, presented with marked neck pain, and were treated with external immobilization. All patients had good clinical outcome. The mechanism of injury is hyperflexion with rotation. Isolated unilateral alar ligament rupture is a diagnosis made by excluding associated fracture, dislocation, or disruption of other major ligamentous structures in the craniovertebral junction. CT and MRI are essential in establishing the diagnosis. External immobilization is adequate treatment.

Symptom clusters in patients with advanced-stage cancer referred for palliative radiation therapy in an outpatient setting.

PURPOSE: The aim of this study was to explore the presence of symptom clusters in patients with advanced cancer. PATIENTS AND METHODS: Patients with metastatic cancer referred to an outpatient palliative radiation therapy clinic were asked to rate their symptom distress using the Edmonton Symptom Assessment Scale (ESAS). Baseline demographic data were obtained. To determine interrelationships between symptoms, a principal component analysis with "varimax rotation" was performed on the 9 ESAS symptoms. RESULTS: Between January 1999 and January 2002, a total of 1296 patients with metastases provided complete baseline data on the ESAS. The most common primary cancer sites were lung, breast, and prostate. Fatigue was the highest scored symptom, followed by poor sense of well-being, pain, lack of appetite, and drowsiness. The 4 most prevalent symptoms were poor sense of well-being (92.7%), fatigue (92.2%), drowsiness (79.7%), and anxiety (78.7%). Three symptom clusters were found. Cluster 1 included lack of appetite, nausea, poor sense of well-being, and pain. Cluster 2 included fatigue, drowsiness, and shortness of breath. Cluster 3 included anxiety and depression. CONCLUSION: More work needs to be done on symptom cluster research, especially in setting a consensus in methodology.

Symptom clusters in cancer patients with bone metastases.

PURPOSE: The purpose of this study is to explore whether bone pain "clusters" with other symptoms in patients with bone metastases. MATERIALS AND METHODS: Patients with bone metastases referred to a palliative radiotherapy clinic were asked to rate their symptom distress using the Edmonton Symptom Assessment Scale (ESAS). Analgesic consumption during the previous 24 h was captured at initial consultation. To determine interrelationships between symptoms, a principal component analysis (PCA) with "varimax rotation" was performed on the nine ESAS symptoms. This study defined a "symptom cluster" as two or more symptoms that occur together, are stable, and are relatively independent of other clusters. Patients were followed 1, 2, 4, 8, and 12 weeks post-radiation treatment by telephone. Statistical analysis was performed at each time point for both responders and nonresponders to radiation (response was defined in accordance to the International Bone Metastases Consensus Working Party). RESULTS: Five hundred eighteen patients with bone metastases provided complete baseline data using the ESAS. The four most prevalent symptoms were poor sense of well-being (93.5%), fatigue (92.3%), pain (84.1%), and drowsiness (81.8%). Three clusters were identified and accounted for 66% of the total variance at baseline. Cronbach's alpha coefficient demonstrated high internal reliability in the clusters, with a coefficient ranging from 0.61 to 0.81. It was observed that the clusters changed post-radiation in both responders and nonresponders and that pain clustered with different symptoms (or remained a separate symptom in responders). In nonresponders, three symptom clusters were consistently present, except in week 8. CONCLUSION: Radiotherapy influenced the structure of symptom clusters in both responders and nonresponders. There was evidence that pain clustered out in responders of radiation to pain. It was found that pain clustered with fatigue, drowsiness, and poor sense of well-being at baseline. However, these findings must be heeded with caution, as more work is needed to clearly define symptom clusters and to understand the effects of radiation in the symptom experience of patients with bone metastases.

Palliative radiotherapy trials for bone metastases: a systematic review.

PURPOSE: The objective is to update previous meta-analyses with a systematic review of randomized palliative radiotherapy (RT) trials comparing single fractions (SFs) versus multiple fractions (MFs). METHODS: The analysis includes all published reports from randomized trials comparing SF or MF schedules for the treatment of painful bone metastases with localized RT. A systematic review was performed using the random-effects model with Review Manager version 4.1 (Cochrane Collaboration, Oxford, UK). The odds ratio and 95% CI were calculated for each trial and presented in a forest plot. RESULTS: A total of 16 randomized trials from 1986 onward were identified. For intention-to-treat patients, the overall response (OR) rates for pain were similar for SF at 1,468 (58%) of 2,513 patients and MF RT at 1,466 (59%) of 2,487 patients. The complete response (CR) rates for pain were 23% (545 of 2,375 patients) for SF and 24% (558 of 2,351 patients) for MF RT. No significant differences were found in response rates. Trends showing an increased risk for SF RT arm patients in terms of pathological fractures and spinal cord compressions were observed, but neither were statistically significant (P = .75 and P = .13, respectively). The likelihood of re-treatment was 2.5-fold higher (95% CI, 1.76 to 3.56) in SF RT arm patients (P < .00001). Repeated analysis of these end points, excluding dropout patients, did not alter the conclusions. Generally, no significant differences with respect to acute toxicities were observed between the arms. CONCLUSION: No significant differences in the arms were observed for overall and CR rates in both intention-to-treat and assessable patients. However, a significantly higher re-treatment rate with SFs was evident.

Involvement of family physicians in the care of cancer patients seen in the palliative Rapid Response Radiotherapy Program.

PURPOSE: It is important for cancer patients to maintain continuity of care with their family physician (FP) while being followed at the cancer center. The primary objective of this study was to determine the perception of patients seen in the palliative Rapid Response Radiotherapy Program (RRRP) on FP involvement in their cancer care. Secondary objectives were to identify factors predicting for perceived FP involvement in patient cancer care. PATIENTS AND METHODS: Consecutive patients were approached for study enrollment at the time of RRRP visit and asked to complete a 15-item survey. RESULTS: Three hundred sixty-five patients were accrued over 15 months. Ninety-eight percent had an FP, and 43% felt their FP was involved in their cancer care. Eighty percent of patients were satisfied with the overall medical care provided by their FP, and 71% had been with their FP for > or = 5 years. The most common reason patients gave for perceiving limited FP involvement was the medical oncologist looking after all of their cancer needs. Multivariate analysis found that satisfaction with overall medical care provided by the FP, shorter time since last FP visit, seeing the FP since cancer diagnosis, and FP providing on-call service for after-hour emergencies all significantly predicted for patients perceiving FP involvement in their cancer care. CONCLUSION: Less than half of patients surveyed perceived their FP as involved in their cancer care. Encouraging continuity of care between patients and FPs may allow for easier transition of care back to the FP once palliative treatment at the cancer center has finished and help facilitate end-of-life planning.