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PubMed | Center for Radiation Oncology, University of Lausanne, University of Zürich, ETH Zurich and 3 more.
Type: | Journal: Cancer treatment reviews | Year: 2016

Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer theranostic vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the magic bullet conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this magic (nano)bullet and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics.


Datta N.R.,Center for Radiation Oncology | Heuser M.,Center for Radiation Oncology | Samiei M.,International Atomic Energy Agency | Shah R.,Online Telemedicine Research Institute | And 3 more authors.
Telemedicine and e-Health | Year: 2015

Globally, new cancer cases will rise by 57% within the next two decades, with the majority in the low-and middle-income countries (LMICs). Consequently, a steep increase of about 40% in cancer deaths is expected there, mainly because of lack of treatment facilities, especially radiotherapy. Radiotherapy is required for more than 50% of patients, but the capital cost for equipment often deters establishment of such facilities in LMICs. Presently, of the 139 LMICs, 55 do not even have a radiotherapy facility, whereas the remaining 84 have a deficit of 61.4% of their required radiotherapy units. Networking between centers could enhance the effectiveness and reach of existing radiotherapy in LMICs. A teleradiotherapy network could enable centers to share and optimally utilize their resources, both infrastructure and staffing. This could be in the form of a three-tier radiotherapy service consisting of primary, secondary, and tertiary radiotherapy centers interlinked through a network. The concept has been adopted in some LMICs and could also be used as a "service provider model," thereby reducing the investments to set up such a network. Teleradiotherapy networks could be a part of the multipronged approach to address the enormous gap in radiotherapy services in a cost-effective manner and to support better accessibility to radiotherapy facilities, especially for LMICs. © 2015, Mary Ann Liebert, Inc.


Datta N.R.,Kantonsspital Aarau AG | Samiei M.,International Atomic Energy Agency | Bodis S.,Center for Radiation Oncology | Bodis S.,University of Zürich
International Journal of Radiation Oncology Biology Physics | Year: 2015

Purpose The economic viability of establishing a state-funded radiation therapy (RT) infrastructure in low- and middle-income countries (LMICs) in accordance with the World Bank definition has been assessed through computation of a return on investment (ROI). Methods and Materials Of the 139 LMICs, 100 were evaluated according to their RT facilities, gross national income (GNI) per capita, and employment/population ratio. The assumption was an investment of US$5 million for a basic RT center able to treat 1000 patients annually. The national breakeven points and percentage of ROI (%ROI) were calculated according to the GNI per capita and patient survival rates of 10% to 50% at 2 years. It was assumed that 50% of these patients would be of working age and that, if employed and able to work after treatment, they would contribute to the country's GNI for at least 2 years. The cumulative GNI after attaining the breakeven point until the end of the 15-year lifespan of the teletherapy unit was calculated to estimate the %ROI. The recurring and overhead costs were assumed to vary from 5.5% to 15% of the capital investment. Results The %ROI was dependent on the GNI per capita, employment/population ratio and 2-year patient survival (all P<.001). Accordingly, none of the low-income countries would attain an ROI. If 50% of the patients survived for 2 years, the %ROI in the lower-middle and upper-middle income countries could range from 0% to 159.9% and 11.2% to 844.7%, respectively. Patient user fees to offset recurring and overhead costs could vary from "nil" to US$750, depending on state subsidies. Conclusions Countries with a greater GNI per capita, higher employment/population ratio, and better survival could achieve a faster breakeven point, resulting in a higher %ROI. Additional factors such as user fees have also been considered. These can be tailored to the patient's ability to pay to cover the recurring costs. Certain pragmatic steps that could be undertaken to address these issues are discussed in the present study. © 2015 Elsevier Inc. All rights reserved.


PubMed | GROW School for Oncology and Developmental Biolog, Center for Radiation Oncology, Coordinating Center, University of Zürich and 4 more.
Type: Journal Article | Journal: Radiation oncology (London, England) | Year: 2017

To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC).Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if 90% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54-70Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5. Primary trial endpoint was dose-limiting toxicity (DLT), as specifically defined for 17 clinical and nine laboratory parameters as grade 3 or 4 toxicity (CTCAE vs. 3). The threshold to declare a dose level as maximum tolerated dose (MTD) was defined as a DLT rate of 16.7% in dose levels 1-3, and 10% in dose levels 4-5. Best objective response of target liver lesions and adverse events (AEs) were assessed as secondary endpoints.The trial was terminated early in DL 3 due to low accrual. Nineteen patients were recruited. Fifteen patients were evaluable for the primary and 18 for the secondary endpoints. Maximum tolerated dose was not reached. One patient in dose level 1, and one patient in dose level 2 experienced DLT (lipase > 5xULN, and neutrophils <500/L respectively). However, dose level 3 (62Gy) was completed, with no DLTs in 3 patients. Overall, 56% of patients had a partial response and 28% showed stable disease according to RECIST. No signs of radiation induced liver disease (RILD). Two patients in dose level 3 experienced lymphocytopenia grade 4, with no clinical impact.Conventionally fractionated radiotherapy of 58Gy to even large HCC was safe for patients with CPS A and B. 62Gy was delivered to three patients without any sign of clinically relevant increased toxicity. The maximum tolerated dose could not be determined.ClinicalTrials.gov identifier NCT00777894 , registered October 21st, 2008.


Datta N.R.,Center for Radiation Oncology | Samiei M.,International Consultant | Bodis S.,Center for Radiation Oncology | Bodis S.,University of Zürich
European Journal of Cancer | Year: 2014

Radiotherapy (RT) is required for nearly half of the newly diagnosed cancer patients. To optimise the quality and availability of RT, guidelines have been proposed by European Society for Radiotherapy and Oncology-QUAntification of Radiation Therapy Infrastructure And Staffing Needs (ESTRO-QUARTS) and the International Atomic Energy Agency (IAEA). This study evaluates the present status of RT capacity in Europe and the projected needs by 2020 as per these recommendations. Thirty-nine of the 53 countries, listed in Europe by the UN Statistical Division, whose cancer incidences, teletherapy and human resources were available in the Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN), International Agency for Research on Cancer (IARC) and DIrectory of RAdiotherapy Centres (DIRAC) (IAEA) databases were evaluated. A total of 3550 teletherapy units (TRT), 7017 radiation oncologists (RO), 3685 medical physicists (MP) and 12,788 radiotherapy technologists (RTT) are presently available for the 3.44 million new cancer cases reported annually in these countries. The present infrastructure and human resources in RT are estimated to provide RT access to 74.3% of the patients requiring RT. The current capacity in TRT, RO, MP and RTT when compared with recommended guidelines has a deficit of 25.6%, 18.3%, 22.7% and 10.6%, respectively. Thus, to respond to requirements by 2020, the existing capacity needs to be augmented by an additional 1698 TRTs, 2429 ROs, 1563 MPs and 2956 RTTs. With an imminent rise in cancer incidence, multifaceted strategic planning at national and international levels within a coordinated comprehensive cancer control programme is highly desirable to give adequate access to all patients who require radiotherapy across Europe. Specific steps to address this issue at national and continental levels involving all major stakeholders are proposed. © 2014 Elsevier Ltd. All rights reserved.


Srivastava A.,Medicity | Datta N.R.,Center for Radiation Oncology
World Journal of Clinical Oncology | Year: 2014

Brachytherapy forms an integral part of the radiation therapy in cancer cervix. The dose prescription for intracavitary brachytherapy (ICBT) in cancer cervix is based on Tod and Meredith's point A and has been in practice since 1938. This was proposed at a time when accessibility to imaging technology and dose computation facilities was limited. The concept has been in practice worldwide for more than half a century and has been the fulcrum of all ICBT treatments, strategies and outcome measures. The method is simple and can be adapted by all centres practicing ICBT in cancer cervix. However, with the widespread availability of imaging techniques, clinical use of different dose-rates, availability of a host of applicators fabricated with image compatible materials, radiobiological implications of dose equivalence and its impact on tumour and organs at risk; more and more weight is being laid down on individualised image based brachytherapy. Thus, computed tomography, magnetic-resonance imaging and even positron emission computerized tomography along with brachytherapy treatment planning system are being increasingly adopted with promising outcomes. The present article reviews the evolution of dose prescription concepts in ICBT in cancer cervix and brings forward the need for image based brachytherapy to evaluate clinical outcomes. As is evident, a gradual transition from "point" based brachytherapy to "profile" based image guided brachytherapy is gaining widespread acceptance for dose prescription, reporting and outcome evaluation in the clinical practice of ICBT in cancer cervix. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Mounessi F.S.,University of Munster | Lehrich P.,University of Munster | Haverkamp U.,University of Munster | Willich N.,University of Munster | And 2 more authors.
Strahlentherapie und Onkologie | Year: 2013

Purpose: The goal of the present work was to assess the potential advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3D-CRT) planning in pelvic Ewing's sarcoma. Patients and methods: A total of 8 patients with Ewing sarcoma of the pelvis undergoing radiotherapy were analyzed. Plans for 3D-CRT and IMRT were calculated for each patient. Dose coverage of the planning target volume (PTV), conformity and homogeneity indices, as well as further parameters were evaluated. Results: The average dose coverage values for PTV were comparable in 3D-CRT and IMRT plans. Both techniques had a PTV coverage of V95 > 98 % in all patients. Whereas the IMRT plans achieved a higher conformity index compared to the 3D-CRT plans (conformity index 0.79 ± 0.12 vs. 0.54 ± 0.19, p = 0.012), the dose distribution across the target volumes was less homogeneous with IMRT planning than with 3D-CRT planning. This difference was statistically significant (homogeneity index 0.11 ± 0.03 vs. 0.07 ± 0.0, p = 0.035). For the bowel, Dmean and D1%, as well as V 2 to V60 were reduced in IMRT plans. For the bladder and the rectum, there was no significant difference in Dmean. However, the percentages of volumes receiving at least doses of 30, 40, 45, and 50 Gy (V30 to V50) were lower for the rectum in IMRT plans. The volume of normal tissue receiving at least 2 Gy (V2) was significantly higher in IMRT plans compared with 3D-CRT, whereas at high dose levels (V30) it was significantly lower. Conclusion: Compared to 3D-CRT, IMRT showed significantly better results regarding dose conformity (p = 0.012) and bowel sparing at dose levels above 30 Gy (p = 0.012). Thus, dose escalation in the radiotherapy of pelvic Ewing's sarcoma can be more easily achieved using IMRT. © 2013 Urban & Vogel.


Datta N.R.,Center for Radiation Oncology | Puric E.,Center for Radiation Oncology | Klingbiel D.,Swiss Group for Clinical Cancer Research | Gomez S.,Center for Radiation Oncology | Bodis S.,Center for Radiation Oncology
International journal of radiation oncology, biology, physics | Year: 2016

PURPOSE: To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs).METHODS AND MATERIALS: A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR).RESULTS: Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627 patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5°C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P<.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25-1.96, P<.0001) and 0.22 (95% CI 0.11-0.33, P<.0001), respectively. In 26 single-arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean ± SD dose: 36.7 ± 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively.CONCLUSIONS: Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective and safe palliative treatment option for LRBCs. Copyright © 2016 Elsevier Inc. All rights reserved.


PubMed | University of Zürich and Center for Radiation Oncology
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2016

To propose a roadmap and explore the cost implications of establishing a teleradiotherapy network to provide comprehensive cancer care and capacity building in countries without access to radiation therapy.Ten low-income sub-Saharan countries with no current radiation therapy facilities were evaluated. A basic/secondary radiation therapy center (SRTC) with 2 teletherapy, 1 brachytherapy, 1 simulator, and a treatment planning facility was envisaged at a cost of 5 million US dollars (USD 5M). This could be networked with 1 to 4 primary radiation therapy centers (PRTC) with 1 teletherapy unit, each costing USD 2M. The numbers of PRTCs and SRTCs for each country were computed on the basis of cancer incidence, assuming that a PRTC and SRTC could respectively treat 450 and 900 patients annually.An estimated 71,215 patients in these countries will need radiation therapy in 2020. Stepwise establishment of a network with 99 PRTCs and 28 SRTCs would result in 155 teletherapy units and 96% access to radiation therapy. A total of 310 radiation oncologists, 155 medical physicists, and 465 radiation therapy technologists would be needed. Capacity building could be undertaken through telementoring by networking to various international institutions and professional societies. Total infrastructure costs would be approximately USD 860.88M, only 0.94% of the average annual gross domestic product of these 10 countries. A total of 1.04 million patients could receive radiation therapy during the 15-year lifespan of a teletherapy unit for an investment of USD 826.69 per patient. For the entire population of 218.32 million, this equates to USD 4.11 per inhabitant.A teleradiotherapy network could be a cost-contained innovative health care strategy to provide effective comprehensive cancer care through resource sharing and capacity building. The network could also be expanded to include other allied specialties. The proposal calls for active coordination between all national and international organizations backed up by strong geopolitical commitment and action from all stakeholders.


PubMed | University of Zürich, Swiss Group for Clinical Cancer Research and Center for Radiation Oncology
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2016

To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs).A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR).Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627 patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P<.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25-1.96, P<.0001) and 0.22 (95% CI 0.11-0.33, P<.0001), respectively. In 26 single-arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean SD dose: 36.7 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively.Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective and safe palliative treatment option for LRBCs.

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