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Late effects of cancer therapy

Michael C Milone, Vijay G Bhoj
Adoptive cellular therapy using T cells with tumor specificity derived from either natural T cell receptors (TCRs) or an artificial chimeric antigen receptor (CAR) has reached late phase clinical testing, with two CAR T cell therapies achieving regulatory approval within the United States in 2017. The effective use of these therapies depends upon an understanding of their pharmacology, which is quite divergent from traditional small molecule or biologic drugs. We review the different types of T cell therapy under clinical development, the factors affecting cellular kinetics following infusion, and the relationship between these cellular kinetics and anti-cancer activity...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Ronan L McDermott, John G Armstrong, Pierre Thirion, Mary Dunne, Marie Finn, Cormac Small, Mary Byrne, Carmel O'Shea, Lydia O'Sullivan, Aoife Shannon, Emma Kelly, Dayle J Hacking
TITLE: Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. BACKGROUND & PURPOSE: Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high...
March 13, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Jeff M Michalski, Jennifer Moughan, James Purdy, Walter Bosch, Deborah W Bruner, Jean-Paul Bahary, Harold Lau, Marie Duclos, Matthew Parliament, Gerard Morton, Daniel Hamstra, Michael Seider, Michael I Lock, Malti Patel, Hiram Gay, Eric Vigneault, Kathryn Winter, Howard Sandler
Importance: Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences. Objective: To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer. Design, Setting, and Participants: The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008...
March 15, 2018: JAMA Oncology
Cun-Zhi Lin, Gui-Ling Xiang, Xin-Hong Zhu, Lu-Lu Xiu, Jia-Xing Sun, Xiao-Yuan Zhang
Cancer virotherapy mediated by oncolytic viruses (OV), has emerged as a novel and effective strategy in cancer therapeutics. Preclinical models have demonstrated anticancer activity against numerous types of cancer. Currently, a number of recombinant viruses are in late phase clinical trials, many of which have demonstrated promising results regarding the safety and reliability of the treatments, particularly when combined with standard antineoplastic therapies. In addition to molecular-targeted therapeutics, genetic engineering of the viruses allows functional complementation to chemotherapy or radiotherapy agents...
April 2018: Oncology Letters
Katyayani Tatiparti, Samaresh Sau, Kaustubh A Gawde, Arun K Iyer
Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of the logical and economical approaches is to develop a tumor hypoxia-targeting drug formulation platform for selective delivery of payload to the drug-resistant and invasive cell population of TNBC tumors...
March 13, 2018: International Journal of Molecular Sciences
Elif Guler, Nilgun Col, Mithat Buyukcelik, Ayse Balat
AIM: In recent years, survival rates of childhood cancers have significantly increased, and occurrence of long-term adverse late effects (eg, insulin resistance, diabetes mellitus, metabolic syndrome, hypertension) has become increasingly important. Early diagnosis of obesity/hypertension in childhood is essential to avoid morbidity in the adulthood. Therefore, this study was aimed to determine the blood pressure (BP) profile by ambulatory BP monitoring (ABPM) method, and prevalence of hypertension, obesity, abdominal obesity among childhood cancer survivors...
March 12, 2018: Pediatric Hematology and Oncology
Viktor Smanykó, Norbert Mészáros, Mihály Újhelyi, Georgina Fröhlich, Gábor Stelczer, Tibor Major, Zoltán Mátrai, Csaba Polgár
INTRODUCTION AND AIM: To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. METHOD: Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4-24) catheters were implanted into the tumor bed intraoperatively...
March 2018: Orvosi Hetilap
Kim I Cao, Flore Salviat, Fatima Laki, Marie-Christine Falcou, Matthieu Carton, Philip Poortmans, Alain Fourquet, Youlia M Kirova
OBJECTIVES: The aim of this study was to assess efficacy, tolerability, and the impact of comorbidities on outcomes in older women treated by radiation therapy (RT) for non-metastatic breast cancer. MATERIALS AND METHODS: Women aged ≥70 years at diagnosis who received postoperative RT for primary non-metastatic BC between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient. We analyzed overall survival (OS), progression free survival (PFS), and acute and late toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) v3...
March 7, 2018: Journal of Geriatric Oncology
Sarah Falk
Pain is a major complication for cancer patients significantly compromising their quality of life. Current treatment is far from optimal and particularly bone-related cancer pain poses an increasing clinical and socio-economical problem. Connexins, key proteins in cell-cell communication, have the potential to affect cancer-induced bone pain at multiple levels, including nociceptive signaling and bone degradation. This study tested the analgesic potential of carbenoxolone, a broad-acting connexin blocker, in a mouse model of cancer-induced bone pain...
March 6, 2018: Pain
Michael Chao, Huong Ho, Yee Chan, Alwin Tan, Trung Pham, Damien Bolton, Andrew Troy, Catherine Temelcos, Shomik Sengupta, Kevin McMillan, Chee Wee Cham, Madalena Liu, Wei Ding, Brindha Subramanian, Jason Wasiak, Daryl Lim Joon, Sandra Spencer, Nathan Lawrenstchuk
OBJECTIVE: The purpose of this study was to report on the dosimetric benefits and late toxicity outcomes following injection of a hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy. METHODS: A total of 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the peri-rectal space prior to intensity modulated radiation therapy (IMRT) or volumetric modulated radiation therapy (VMAT)...
March 9, 2018: BJU International
Alessandro Magli, Eugenia Moretti, Annarita Tullio, Gianluca Giannarini, Fabrizio Tonetto, Mauro Urpis, Margherita Crespi, Claudio Foti, Agnese Prisco, Margherita Polsinelli, Gioacchino De Giorgi, Giulia Bravo, Paolo Scalchi, Marco Trovò
OBJECTIVE: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. MATERIALS AND METHODS: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012...
March 8, 2018: Prostate Cancer and Prostatic Diseases
Joshua L Pierce, A Lindsay Frazier, James F Amatruda
Germ cell tumors (GCTs) arising in infants, children, and adolescents present a set of special challenges. GCTs make up about 3% of malignancies in children aged 0-18 and nearly 15% of cancers in adolescents. Epidemiologic and molecular evidence suggests that GCTs in young children likely represent a distinct biologic group as compared to GCTs of older adolescents and adults. Despite this difference, pediatric GCTs are typically treated with cisplatin-based multiagent regimens similar to those used in adults...
2018: Advances in Urology
Deborah Repullo, Marie Diaz, Stéphane Holbrechts, Maria Gomez-Galdón, Dirk Van Gestel, Ali Bohlok, Gabriel Liberale, Vincent Donckier
BACKGROUND: The development of a second primary tumor is a potential late side effect of radiotherapy. Particularly, an increased risk of secondary cancers, mostly of digestive or breast origin, has been observed in patients treated with high-dose radiotherapy for Wilms tumor (WT) in childhood. However, hepatocellular carcinoma (HCC) has been very rarely described as a potentially radiotherapy-induced tumor. We describe the case of a patient with an aggressive HCC 50 years after the treatment of a WT...
March 7, 2018: World Journal of Surgical Oncology
Filip Janku, Timothy A Yap, Funda Meric-Bernstam
The PI3K-AKT-mTOR pathway is one of the most frequently dysregulated pathways in cancer and, consequently, more than 40 compounds that target key components of this signalling network have been tested in clinical trials involving patients with a range of different cancers. The clinical development of many of these agents, however, has not advanced to late-phase randomized trials, and the antitumour activity of those that have been evaluated in comparative prospective studies has typically been limited, or toxicities were found to be prohibitive...
March 6, 2018: Nature Reviews. Clinical Oncology
Ronny Kalash, Phillip M Pifer, Sushil Beriwal, Scott M Glaser, John A Vargo, Dwight E Heron
Breast cancer represents the second leading cause of brain metastases in women. Once diagnosed, brain metastases have been associated with a rapidly progressive and universally poor prognosis. Breast cancer patients, particularly those with advantageous disease characteristics, may achieve extended survival. This extended life expectancy highlights the importance of effective intracranial treatments that minimize treatment-related late toxicity. Whole brain radiation therapy (WBRT) remains a standard of care palliative option; however, concerns remain regarding the late neurocognitive effects...
December 29, 2017: Curēus
Kosma Woliński, Rafał Czepczyński, Adam Stangierski, Maciej Trojanowski, Magdalena Rewaj-Łosyk, Katarzyna Ziemnicka, Maciej Bączyk, Agnieszka Dyzmann-Sroka, Marek Ruchała
INTRODUCTION: Due to a limited number of hospital beds dedicated to radioiodine therapy (RIT) in some countries, a fractionated dose of radioiodine may be considered as the ablation therapy of differentiated thyroid cancer (DTC). The aim of the study was to compare the late effects of ablation therapy with single and fractionated dose of radioiodine in patients with DTC. PATIENTS AND METHODS: Patients with low-risk DTC referred to our institution 5-16 weeks after thyroidectomy, treated with 2...
March 5, 2018: Endokrynologia Polska
Masoud Najafi, Elahe Motevaseli, Alireza Shirazi, Ghazale Graily, Abolhasan Rezaeyan, Farzad Norouzi, Saeed Rezapoor, Hamid Abdollahi
PURPOSE: Cancer treatment is one of the most challenging diseases in the present era. Among a few modalities for cancer therapy, radiotherapy plays a pivotal role in more than half of all treatments alone or combined with other cancer treatment modalities. Management of normal tissue toxicity induced by radiation is one of the most important limiting factors for an appropriate radiation treatment course. The evaluation of mechanisms of normal tissue toxicity has shown that immune responses especially inflammatory responses play a key role in both early and late side effects of exposure to ionizing radiation (IR)...
March 5, 2018: International Journal of Radiation Biology
Sangkyu Lee, Sarah Kerns, Harry Ostrer, Barry Rosenstein, Joseph O Deasy, Jung Hun Oh
PURPOSE: Late genitourinary (GU) toxicity after radiation therapy limits the quality of life of prostate cancer survivors; however, efforts to explain GU toxicity using patient and dose information have remained unsuccessful. We identified patients with a greater congenital GU toxicity risk by identifying and integrating patterns in genome-wide single nucleotide polymorphisms (SNPs). METHODS AND MATERIALS: We applied a preconditioned random forest regression method for predicting risk from the genome-wide data to combine the effects of multiple SNPs and overcome the statistical power limitations of single-SNP analysis...
January 31, 2018: International Journal of Radiation Oncology, Biology, Physics
Qi Sun, Geng Zong, Damaskini Valvi, Flemming Nielsen, Brent Coull, Philippe Grandjean
BACKGROUND: Emerging evidence suggests that perfluoroalkyl substances (PFASs) are endocrine disruptors and may contribute to the etiology of type 2 diabetes (T2D), but this hypothesis needs to be clarified in prospective human studies. OBJECTIVES: Our objective was to examine the associations between PFAS exposures and subsequent incidence of T2D in the Nurses' Health Study II (NHSII). In addition, we aimed to evaluate potential demographic and lifestyle determinants of plasma PFAS concentrations...
March 1, 2018: Environmental Health Perspectives
Asma Javed, Zaraq Khan, Siobhan T Pittock, Jani R Jensen
Fertility preservation therapies can conserve future reproductive potential for persons facing serious medical diagnoses. With cure rates for childhood cancer reaching almost 80%, quality-of-life concerns for long-term survivors, including future parenting, are becoming more pertinent. Late effects of childhood cancer can be divided into physical, social, psychological, and spiritual domains. Potential loss of fertility threatens the well-being of these children in all these domains. Providers often hesitate to discuss fertility preservation with the patients...
March 2018: Pediatric Endocrinology Reviews: PER
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