Thursday, December 22, 2011

Radiotherapy and "new" drugs - new side effects?

Background and Purpose: Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments.Material and Methods: Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab / trastuzumab / panitumumab / nimotuzumab, bevacizumab, sunitinib / sorafenib / lapatinib / gefitinib / erlotinib / sirolimus, thalidomide / lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Results: Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. Conclusions: The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity.





Postado por No comments:

Socio-economic implications of cancer survivorship: Results from the PROFILES registry

Publication year: 2011
Source: European Journal of Cancer, Available online 21 December 2011
Floortje Mols, Melissa S.Y. Thong, Pauline Vissers, Tamar Nijsten, Lonneke V. van de Poll-Franse
IntroductionThe goal of this large population-based study was to examine the socio-economic implications of cancer survivorship.MethodsIndividuals alive and diagnosed with colorectal cancer and melanoma between 1998 and 2007 or Hodgkin lymphoma, non-Hodgkin lymphoma or multiple myeloma between 1999 and 2008 as registered in the Eindhoven Cancer Registry received a questionnaire on work changes and problems with obtaining a new (or extended) health care insurance, life insurance or a home loan; 70% (n = 2892) responded.ResultsResults showed that 28% of all cancer patients experienced changes in their work situation after cancer. Most of them switched to part-time work or stopped working entirely. Patients (3.4%) who tried to obtain a different or upgrade their health care insurance experienced problems and in most cases, these were eventually resolved. Problems with life insurance were somewhat more common with 18% of those who tried to obtain a life insurance experiencing problems. The majority of these patients was rejected by the insurance company (61%) or was accepted at a higher premium (22%). Of the 21% who tried to obtain a home loan, 9% experienced problems. However, 22.2% got accepted eventually, 27.8% got accepted but at a higher mortgage payment and 22.2% got rejected but were eventually accepted by another bank.ConclusionsAlmost a third of cancer survivors experienced changes in their work situation after cancer. Problems with obtaining health insurance, life insurance and home loans were also common.





Postado por No comments:

Tuesday, December 20, 2011

Analysis of Dose at the Site of Second Tumor Formation After Radiotherapy to the Central Nervous Sys

Purpose: Second tumors are an uncommon complication of multimodality treatment of childhood cancer. The present analysis attempted to correlate the dose received as a component of primary treatment and the site of the eventual development of a second tumor.Methods and Materials: We retrospectively identified 16 patients who had received radiotherapy to sites in the craniospinal axis and subsequently developed a second tumor. We compared the historical fields and port films of the primary treatment with the modern imaging of the second tumor locations. We classified the location of the second tumors as follows: in the boost field; marginal to the boost field, but in a whole-brain field; in a whole-brain field; marginal to the whole brain/primary treatment field; and distant to the field. We divided the dose received into 3 broad categories: high dose (>45 Gy), moderate dose (20–36 Gy), and low dose (<20 Gy).Results: The most common location of the second tumor was in the whole brain field (57%) and in the moderate-dose range (81%).Conclusions: Our data contradict previous publications that suggested that most second tumors develop in tissues that receive a low radiation dose. Almost all the second tumors in our series occurred in tissue within a target volume in the cranium that had received a moderate dose (20–36 Gy). These findings suggest that a major decrease in the brain volume that receives a moderate radiation dose is the only way to substantially decrease the second tumor rate after central nervous system radiotherapy.





Postado por No comments:

Apoptosis induction and tumor cell repopulation: The yin and yang of radiotherapy

The induction of tumor cell death is a central goal of radiotherapy. Surprisingly, a recent study sheds new light on this process, and the results presented by Huang et al. strongly question the benefit of radiation-induced apoptosis for the outcome of cancer radiotherapy.





Postado por No comments:

Monday, December 19, 2011

Independent prognostic value of pre-treatment 18-FDG-PET in high-grade gliomas

Abstract  
The prognostic value of PET with (18F)-fluoro-2-deoxy-d-glucose (FDG) has been shown in high-grade gliomas (HGG), but not compared with consensual prognostic factors. We sought to evaluate the independent predictive value of pre-treatment FDG-PET on overall (OS) and event-free survival (EFS). We retrospectively analyzed 41 patients with histologically-confirmed HGG (31 glioblastomas and 10 anaplastic gliomas). The pre-treatment uptake of FDG was assessed qualitatively by five-step visual metabolic grading, and quantitatively by the ratio between the tumor and contralateral maximal standardized uptake value (T/CL). EFS and OS following PET were compared with FDG uptake by univariate analysis, and by two multivariate analyses: one including main consensual prognostic factors (age, KPS, extent of surgery and histological grade), and the other including the classification system of the Radiation Therapy Oncology Group (Recursive Partitioning Analysis, RPA). Median OS and EFS were 13.8 and 7.4 months, respectively, for glioblastomas, and over 25.8 and 12 months, respectively, for anaplastic gliomas (P = 0.040 and P = 0.027). The T/CL ratio predicted OS in the entire group [P = 0.003; Hazard Ratio (HR) = 2.3] and in the glioblastoma subgroup (P = 0.018; HR = 2), independently of age, Karnofsky performance status, histological grade, and surgery, and independently of RPA classification. T/CL ratio tended to predict EFS in the whole group (P = 0.052). The prognostic value of visual metabolic grade on OS was less significant than T/CL ratio, both in the entire group and in the glioblastoma subgroup (P = 0.077 and P = 0.059). Quantitative evaluation of the ratio between the maximal tumor and contralateral uptake in pre-treatment FDG-PET provides significant additional prognostic information in newly-diagnosed HGG, independently of consensual prognostic factors.

  • Content Type Journal Article
  • Category Clinical Study - Patient Study
  • Pages 1-9
  • DOI 10.1007/s11060-011-0771-6
  • Authors
    • Cécile Colavolpe, APHM, Hôpital de la Timone, Service Central de Biophysique et Médecine Nucléaire, 13005 Marseille, France
    • Philippe Metellus, APHM, Hôpital de la Timone, Service de Neurochirurgie, 13005 Marseille, France
    • Julien Mancini, APHM, Hôpital de la Timone, Service de Santé Publique et d'Information Médicale, 13005 Marseille, France
    • Maryline Barrie, APHM, Hôpital de la Timone, Unité de Neuro-Oncologie, 13005 Marseille, France
    • Céline Béquet-Boucard, APHM, Hôpital de la Timone, Unité de Neuro-Oncologie, 13005 Marseille, France
    • Dominique Figarella-Branger, Aix-Marseille Université, UMR 911 Inserm, 13005 Marseille, France
    • Olivier Mundler, APHM, Hôpital de la Timone, Service Central de Biophysique et Médecine Nucléaire, 13005 Marseille, France
    • Olivier Chinot, Aix-Marseille Université, UMR 911 Inserm, 13005 Marseille, France
    • Eric Guedj, APHM, Hôpital de la Timone, Service Central de Biophysique et Médecine Nucléaire, 13005 Marseille, France





Postado por No comments:

Medulloblasoma: challenges for effective immunotherapy

Abstract  
For medulloblastoma patients, the current therapeutic paradigm of surgery followed by radiation and chemotherapy can lead to long-term remission. However, the sequelae of treatment can be very debilitating, particularly in young children. Immunotherapy is an attractive treatment approach to optimize the targeting of tumor cells while sparing the vulnerable surrounding brain that is still developing in children. Understanding the relationship between medulloblastoma and the immune system is critical to develop effective immunologic-based treatment strategies for these patients. This review focuses on current knowledge of tumor immunology and the factors that contribute to the lack of immune system recognition of these tumors. The specificity of tumor antigens present in medulloblastoma is also discussed along with a summary of early clinical immunotherapy results.

  • Content Type Journal Article
  • Category Topic Review
  • Pages 1-10
  • DOI 10.1007/s11060-011-0776-1
  • Authors
    • Adam M. Sonabend, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA
    • Alfred T. Ogden, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA
    • Lisa M. Maier, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA
    • David E. Anderson, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA
    • Peter Canoll, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA
    • Jeffrey N. Bruce, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA
    • Richard C. E. Anderson, Department of Neurological Surgery, Neurological Institute, New York Presbyterian Columbia University, 710 West 168th Street, New York, NY 10032, USA





Postado por No comments:

Saturday, December 17, 2011

RTOG Activates Study To Determine Best Treatment Strategies For Patients With Glioma Brain Tumors

Treatment remains controversial for patients diagnosed with a low-risk, low-grade glioma (LGG) brain tumor. These patients have significantly better prognosis than patients diagnosed with more aggressive high-grade glioma, and their clinical care often involves ongoing observation for tumor changes with imaging studies...





Postado por No comments:

Spinal radiosurgery - efficacy and safety after prior conventional radiotherapy

Background: Conventional external beam radiotherapy is a standard procedure for treatment of spinal metastases. In case of progression spinal cord tolerance limits further radiotherapy in pre-irradiated areas. Spinal stereotactic radiotherapy is a non-invasive option to re-treat pre-irradiated patients. Nevertheless, spinal radiosurgery results in relevant dose deposition within the myelon with potential toxicity. Aim of the study was to retrospectively analyse the efficacy and feasibility for salvage radiosurgery of spinal metastases. Methods: During a period of 4 years (2005-2009) 70 lesions in 54 patients were treated in 60 radiosurgery sessions and analysed. Clinical (pain, sensory and motor deficit) and radiological (CT/MRI) follow-up data were collected prospectively after radiosurgery. Pain - as main symptom - was classified by the Visual Analogue Scale (VAS) score. Every patient received single session radiosurgery after having been treated first-line with conventionally fractionated radiotherapy. Kaplan-Meier method and life tables were used to analyse freedom from local failure and overall survival. Results: At a median follow-up of 14.5 months the actuarial rates of freedom from local failure at 6/12/18 months were 93%, 88% and 85%, respectively. The median radiosurgery dose was 1 x 18 Gy (range 10-28 Gy) to the median 70% isodose. The VAS score of patients with pain (median 6) dropped significantly (median 4, p=0.002). In 6 out of 7 patients worse sensory or motor deficit after SRS was caused by local or distant failures (diagnosed by CT/MRI). One patient with metastatic renal cell carcinoma developed a progressive complete paraparesis one year after the last treatment at lumbar level L3. Due to multiple surgery and radiosurgery treatments at the lumbar region and further local progression, the exact reason remained unclear. Apart from that, no CTC grade III or higher toxicity has been observed. Conclusions: By applying spinal radiosurgery relevant radiation doses can be limited to small parts of the myelon. This prevents myelopathic side effects and makes it an effective and safe treatment option for well-suited patients. Especially for previously irradiated patients with local failure or pain salvage SRS represents a valuable treatment option with high local control rates, low toxicity and significant pain reduction.





Postado por No comments:

Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the centra

Abstract

BACKGROUND:

The objective of this study was to describe the clinical and pathologic features and to identify prognostic factors in patients with atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS).

METHODS:

Patients aged <18 years with newly diagnosed CNS AT/RT who were treated in France between 1998 and 2008 were retrospectively identified. The study included all patients who had a diagnosis of AT/RT confirmed by pathologic review, including immunostaining for INI 1, tumor protein 53 (p53), β-catenin, claudin-6, and Ki-67 and analysis for SMARCB1/hSNF5/INI1 mutation.

RESULTS:

Fifty-eight patients with confirmed AT/RT were eligible for the current analysis. The median age at diagnosis was 1.4 years (range, 14 days to 8.5 years). The site of the primary tumor was supratentorial in 26 patients, infratentorial in 28 patients and spinal in 4 patients. Loss of INI1 nuclear expression was observed in 49 of 50 evaluable tumors. Positive claudin-6 was observed in 37 of 42 assessed tumors and, in 12 of those tumors, the staining was strong and diffuse. Positive nuclear immunoreactivity for β-catenin was observed in 24 of 44 tumors, and P53 was overexpressed in 31 of 44 tumors. Primary adjuvant therapy included chemotherapy in 47 patients and radiotherapy in 16 patients. The median follow-up was 58 months (range, 9-125 months), and the median survival was 9 months. Multivariate analysis identified age <2 years (P = .01), metastasis at diagnosis (P = .03), and strong immunopositivity for claudin-6 (P = .03) as prognostic factors for the risk of death.

CONCLUSIONS:

AT/RT tumors in children carry a dismal prognosis. Age <2 years, metastasis at diagnosis, and strong claudin-6 positivity appeared to be independent prognostic factors for outcome. Cancer 2012;. © 2011 American Cancer Society.






Postado por No comments:

Yoga for persistent fatigue in breast cancer survivors

Abstract

BACKGROUND:

Cancer-related fatigue afflicts up to 33% of breast cancer survivors, yet there are no empirically validated treatments for this symptom.

METHODS:

The authors conducted a 2-group randomized controlled trial to determine the feasibility and efficacy of an Iyengar yoga intervention for breast cancer survivors with persistent post-treatment fatigue. Participants were breast cancer survivors who had completed cancer treatments (other than endocrine therapy) at least 6 months before enrollment, reported significant cancer-related fatigue, and had no other medical conditions that would account for fatigue symptoms or interfere with yoga practice. Block randomization was used to assign participants to a 12-week, Iyengar-based yoga intervention or to 12 weeks of health education (control). The primary outcome was change in fatigue measured at baseline, immediately post-treatment, and 3 months after treatment completion. Additional outcomes included changes in vigor, depressive symptoms, sleep, perceived stress, and physical performance. Intent-to-treat analyses were conducted with all randomized participants using linear mixed models.

RESULTS:

Thirty-one women were randomly assigned to yoga (n = 16) or health education (n = 15). Fatigue severity declined significantly from baseline to post-treatment and over a 3-month follow-up in the yoga group relative to controls (P = .032). In addition, the yoga group had significant increases in vigor relative to controls (P = .011). Both groups had positive changes in depressive symptoms and perceived stress (P < .05). No significant changes in sleep or physical performance were observed.

CONCLUSIONS:

A targeted yoga intervention led to significant improvements in fatigue and vigor among breast cancer survivors with persistent fatigue symptoms. Cancer 2012;. © 2011 American Cancer Society.






Postado por No comments:
Subscribe to: Posts (Atom)