Pain response and quality of life assessment in patients with moderate/severe neuropathic pain due to bone metastasis undergoing treatment with palliative radiotherapy and tapentadol: A prospective multicentre pilot study.

INTRODUCTION: To assess pain response rate (RR) and quality of life (QoL), in patients with moderate/severe neuropathic pain (NP) due to bone metastasis (BM) undergoing palliative 3D radiotherapy plus tapentadol. METHODS: We conducted a prospective multicentre pilot study. Patients were assessed before radiotherapy using the validated questionnaire (Douleur Neuropathique en 4 questions). Response to radiotherapy (8 Gy-30 Gy/1-10fr) at one and two months was assessed according the International Bone Metastases Consensus criteria. INCLUSION CRITERIA: radiological evidence of BM, NP according to DN4 (cut-off score ≥ 4), no spinal cord compression, worst pain score ≥ 5/10. Nonparametric Mann-Whitney U test compared changes in QoL among response groups. RESULTS: Seventeen patients (13 men, 4 woman), median age 67 years (42-81), were included. Pre-treatment median pain severity was 7.5 (5-10). Median dose of tapentadol administered before radiotherapy was 100 mg/24 h (100-300 mg). Overall RR 1 month after radiotherapy was 10/16 = 62.5%: 3/16 (18.8%) achieving a complete response (CR) and 7/16 (43.8%) a partial response (PR). Overall RR 2 months after RT was 5/10 (50%): 10% a CR and 40% a PR. ITT RR for this study at 1 and 2 months was 10/17 = 59% and 5/17 = 29%, respectively. Patients responding to radiotherapy had significant improvement in EORTC QLQ-C30 emotional functioning (EF) (p = 0.025) and fatigue symptom scale scores (p = 0.035) one month after radiotherapy. Painful site symptom QLQ-BM22 scores improved 2 months after radiotherapy (p = 0.024). CONCLUSIONS: Palliative radiotherapy plus tapentadol shows an acceptable pain response and QoL improvement especially regarding EF, fatigue and painful site symptom scales in patients with moderate/severe NP due to BM. Therefore, it could be an alternative to manage NP in daily practice.

Results of short term radiotherapy followed by radical surgery for rectal cancer: A long-term unicenter observational study. / Resultados de la radioterapia de ciclo corto seguida de cirugía radical en el cáncer de recto: estudio unicéntrico y observacional a largo plazo.

INTRODUCTION: Short-term radiotherapy (STR) for rectal cancer (RC) has rarely been used in Spain. The aim of the present study is to describe oncological results after RTC and surgery for RC. METHODS: This is a retrospective analysis of a consecutive series of patients treated with STR and surgery for RC (1999-2012). Epidemiological data, staging, complications of STR, STR-surgery interval, surgical approach, rate of anastomotic/perineal wound dehiscence, and pathological data (regression degree and staging) were collected. Global survival, disease free survival, local recurrence rate and incidence of toxicity, response and complications of combined treatment are reported. RESULTS: Of 1229 patients treated, 209 patients received STR and surgery. The median follow-up was 6.2 years. Mean age was 68 years and 66% of the patients were men. A total of 88% were cT3-4 and 44% cN+17 (8.1%) patients had resectable synchronous metastases. Acute and chronic toxicity due to STR was <5%. In 75% of the cases the STR-surgery interval was <15 days, and in 9%> 4 weeks. Seven patients (3.3%) presented complete response. Nine (4.3%) patients presented an local recurrence rate. Global survival at 5, 10 and 15 years was 67.8, 49.2 and 37.5%, respectively. Disease free survival at 5, 10 and 15 years was 66.1, 47.1 and 33%, respectively. CONCLUSIONS: The results compare favorably with multicentric historical series. STR offers certain advantages that could be increased by increasing the STR-surgery interval and/or interspersed with sequential chemotherapy.

Cognitive Function in Patients With Prostate Cancer Receiving Luteinizing Hormone-Releasing Hormone Analogues: A Prospective, Observational, Multicenter Study.

PURPOSE: The effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in prostate cancer (PCa) patients is not well understood. We evaluated changes in CP after 6 months of medical castration with luteinizing hormone-releasing hormone (LHRH) analogues. METHODS AND MATERIALS: We performed a prospective, observational, multicenter, open-label study of PCa patients scheduled to receive LHRH analogues for ≥6 months. We assessed 4 domains of CP at baseline and after 6 months of ADT: (1) working memory, assessed with the Wechsler Adult Intelligence Scale III (WAIS III) Digit Span subtest; (2) visual memory, assessed with an ad hoc visual memory test; (3) visuospatial ability, assessed with the Judgment of Line Orientation test and Mental Rotation of Three-Dimensional Objects test; and (4) nonverbal analytical reasoning, assessed with the WAIS III Matrix Reasoning test. Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test whereas 63 (20.4%) experienced significant changes on ≥1 test. Most of these patients showed a change on only 1 test, distributed evenly between improvement (58 patients, 18.8%) and worsening (56 patients, 18.2%). For individual tests, most patients (87.8%-91.8%) had no change from baseline; however, the significant changes (improvement vs deterioration) were as follows: WAIS III Digit Span subtest (6.3% vs 5.9%), visual memory (5.3% vs 5.7%), Judgment of Line Orientation test (5.3% vs 4.5%), Mental Rotation of Three-Dimensional Objects test (4.1% vs 4.1%), and WAIS III Matrix Reasoning test (4.8% vs 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.

Resultados de la radioterapia de ciclo corto seguida de cirugía radical en el cáncer de recto: estudio unicéntrico y observacional a largo plazo / Results of short term radiotherapy followed by radical surgery for rectal cancer: A long-term unicenter observational study

Introducción: La radioterapia preoperatoria corta (RTC) para el tratamiento del cáncer de recto (CR) ha sido poco utilizada en España. El objetivo del presente trabajo es describir los resultados oncológicos tras tratamiento con RTC y cirugía por CR. Métodos: Estudio retrospectivo que incluye una serie consecutiva de pacientes tratados por CR (1999-2012). Se recogieron datos epidemiológicos, estadificación, complicaciones de la RTC, intervalo RTC-cirugía, abordaje quirúrgico, tasa de dehiscencia de anastomosis o herida perineal e histológicos (grado de regresión y estadificación). Se analizan la supervivencia global, supervivencia libre de enfermedad, tasa de recurrencia local e incidencia de toxicidad, respuesta y complicaciones del tratamiento combinado con RTC y cirugía. Resultados: De 1.229 pacientes tratados, 209 pacientes recibieron RTC y cirugía. La mediana de seguimiento fue de 6,2 años. La edad media fue de 68 años y el 66% fueron hombres. El 88% eran cT3-4 y el 44% cN+. Un total de 17 pacientes (8,1%) tenían metástasis síncronas resecables. La toxicidad aguda y crónica por RTC fue inferior al 5%. En el 75% de los pacientes el intervalo RTC-cirugía fue inferior a 15 días y en el 9%, superior a 4 semanas. Fueron 7 los pacientes (3,3%) que presentaron respuesta completa. La mediana de supervivencia fue de casi 10 años. Nueve (4,3%) pacientes presentaron una recurrencia local. La supervivencia global a 5, 10 y 15 años fue del 67,8, 49,2 y 37,5%, respectivamente. La supervivencia libre de enfermedad a 5, 10 y 15 años fue del 66,1; 47,1 y 33%, respectivamente. Conclusiones: Los resultados se comparan favorablemente con las series históricas multicéntricas. La RTC ofrece ciertas ventajas que pueden ampliarse incrementando el intervalo RTC-cirugía o si se intercala con quimioterapia secuencial (AU)

Introduction: Short-term radiotherapy (STR) for rectal cancer (RC) has rarely been used in Spain. The aim of the present study is to describe oncological results after RTC and surgery for RC. Methods: This is a retrospective analysis of a consecutive series of patients treated with STR and surgery for RC (1999-2012). Epidemiological data, staging, complications of STR, STR-surgery interval, surgical approach, rate of anastomotic/perineal wound dehiscence, and pathological data (regression degree and staging) were collected. Global survival, disease free survival, local recurrence rate and incidence of toxicity, response and complications of combined treatment are reported. Results: Of 1229 patients treated, 209 patients received STR and surgery. The median follow-up was 6.2 years. Mean age was 68 years and 66% of the patients were men. A total of 88% were cT3-4 and 44% cN+17 (8.1%) patients had resectable synchronous metastases. Acute and chronic toxicity due to STR was <5%. In 75% of the cases the STR-surgery interval was <15 days, and in 9%> 4 weeks. Seven patients (3.3%) presented complete response. Nine (4.3%) patients presented an local recurrence rate. Global survival at 5, 10 and 15 years was 67.8, 49.2 and 37.5%, respectively. Disease free survival at 5, 10 and 15 years was 66.1, 47.1 and 33%, respectively. Conclusions: The results compare favorably with multicentric historical series. STR offers certain advantages that could be increased by increasing the STR-surgery interval and/or interspersed with sequential chemotherapy (AU)

Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

Short-course preoperative radiotherapy (RT) is widely used in northern Europe for locally advanced resectable rectal cancer, but its role in the era of advanced imaging techniques is uncertain. Here, we reviewed articles and abstracts on SCRT published from 1974 through 2013 with the goal of identifying patients who might be best suited for short-course RT. We included relevant articles comparing surgery with or without preoperative radiation published before and after the advent of total mesorectal excision. We also analyzed two randomized trials directly comparing short-course RT with conventionally fractionated chemoradiation (the Polish Colorectal Study Group and the Trans-Tasman Radiation Oncology Group) that compared short-course RT with conventional chemoradiotherapy. We conclude from our review that short-course RT can be generally applied for operable rectal cancer and produces high rates of pelvic control with acceptable toxicity; it reduces local recurrence rates but does not increase overall survival. SCRT seems to be best used for tumors considered "low risk," i.e., those that are >5 cm from the anal margin, without circumferential margin involvement, and involvement of fewer than 4 lymph nodes. Whether sequential chemotherapy can further improve outcomes remains to be seen, as does the best time for surgery (immediately or 6-8 weeks after RT). We further recommend that selection of patients for short-course RT should be based on findings from magnetic resonance imaging or transrectal ultrasonography.

Current treatment of rectal cancer adapted to the individual patient.

Preoperative radiochemotherapy and total mesorectal excision surgery is a recommended standard therapy for patients with locally advanced rectal cancer. However, some subgroups of patients benefit more than others from this approach. In order to avoid long-term complications of radiation and chemotherapy, efforts are being made to subdivide T3N0 stage using advanced imaging techniques, and to analyze prognostic factors that help to define subgroup risk patients. Long-course radiochemotherapy has the potential of downsizing the tumor before surgery and may increase the chance of sphincter preservation in some patients. Short-course radiotherapy (SCRT), on the other hand, is a practical schedule that better suits patients with intermediated risk tumors, located far from the anal margin. SCRT is also increasingly being used among patients with disseminated disease, before resection of the rectal tumor. Improvements in radiation technique, such as keeping the irradiation target below S2/S3 junction, and the use of IMRT, can reduce the toxicity associated with radiation, specially long-term small bowel toxicity.

Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health.

BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.

Functional characterization of highly adherent CD34+ keratinocytes isolated from human skin.

Compared to murine models, data on cells responsible for the homeostasis of human epidermis are scarce and often contradictory. Given the conflicting results and the availability of clinical grade protocols to purify CD34 cells from a given tissue, we pursued to phenotypically characterize human epidermal CD34+ population. After magnetic separation of whole skin CD34+ and CD34- cell fractions and selection for cells highly adherent to extracellular matrix, both CD34+/- fractions retained the ability to form a stratified epidermis in organotypic cultures and presented similar in vitro migratory phenotypes. However CD34- cells showed higher clonogenic potential and in vitro proliferative capacity. These results indicated that CD34- cell fraction contains stem/early progenitor cells, while CD34+ cells might be a transit-amplifying precursor for hair follicle (HF) sheath cells. The ability to isolate living cells using differential cell adhesion and surface markers provides an opportunity to study cells from different morphological regions of the HF.