Eduardo H. Zubizarreta | International Atomic Energy Agency (original) (raw)

Papers by Eduardo H. Zubizarreta

Journal of medical imaging and radiation oncology, Feb 6, 2021

In partnership with the Regional Co‐operative Agreement for Research, Development and Training Re... more In partnership with the Regional Co‐operative Agreement for Research, Development and Training Related to Nuclear Science and Technology (RCA), the IAEA has been supporting Member States in the Asia and Pacific region to prepare, initiate and expand radiotherapy services safely and effectively. Education and training are essential components in IAEA‐RCA projects and have been delivered through various initiatives both online and offline. In addition to building capacity and enabling technology transfer, these initiatives provided opportunities to foster collaboration at the regional level, leading to the initiation of professional societies and education/training schemes.

Radiotherapy and Oncology, Sep 1, 2018

Radiotherapy and Oncology, May 1, 2020

Background: A high cancer burden exists among indigenous populations worldwide. Canada and Greenl... more Background: A high cancer burden exists among indigenous populations worldwide. Canada and Greenland have similar geographic features that make health service delivery challenging. We sought to describe geographic access to radiotherapy for indigenous populations in both regions. Methods: We used geospatial analyses to calculate distance and travel-time from indigenous communities in Canada and Greenland to the nearest radiotherapy center. We calculated the proportion of indigenous communities and populations residing within a 1 and 2-hour drive of a radiotherapy center in Canada, and compared the proportion of indigenous versus non-indigenous populations residing within each drive-time area. We calculated the potential distance and travel-time saved if radiotherapy was available in northern Canada (Yellowknife and Iqaluit), and Greenland (Nuuk). Results: Median one-way travel from indigenous communities to nearest radiotherapy center in Canada was 268 km (3 h when considering any transportation mode), and 4111 km (6 h by plane) in Greenland. In Canada, 84% and 68% of indigenous communities were outside a 1 and 2-hour drive from a radiotherapy center, respectively. Only 2% of the total population in Canada resided outside a 2-hour drive from a radiotherapy center. However, indigenous peoples were 336 times more likely to live more than a 2-hour drive away, compared to non-indigenous peoples. Nearly 3 million km and 4000 h of travel could be saved over a 10-year period for patients with newly diagnosed cancers in Canada, and 7 million km and 10,000 h in Greenland, if radiotherapy was available in Yellowknife, Iqaluit and Nuuk. Conclusions: Geography is an important barrier to accessing radiotherapy for indigenous populations in Canada and Greenland. A significant disparity exists between indigenous and non-indigenous peoples in Canada. Geospatial analyses can help highlight disparities in access to inform radiotherapy service planning.

Clinical Oncology, Jun 1, 2021

AIMS We describe the absolute and per capita numbers of megavoltage radiotherapy machines (MVMs) ... more AIMS We describe the absolute and per capita numbers of megavoltage radiotherapy machines (MVMs) in Western Africa from 1969 to 2019. MATERIALS AND METHODS Western Africa was defined in accordance with the United Nations' delineation and inclusive of 16 countries. A literature search for publications detailing the number of cobalt-60 machines (COs) and linear accelerators (LINACs) in radiotherapy centres was carried out. Population data from the World Bank Group and crude cancer rates from the International Agency for Research on Cancer were used to calculate ratios of million persons per MVM and MVMs per 1000 cancer cases. RESULTS The numbers of MVMs in Western Africa in 1969, 1979, 1989, 1999 and 2009 were zero, two, three, six and nine, respectively. In 2019 there were 22 MVMs distributed across Ghana (five), Côte d'Ivoire (two), Mali (one), Mauritania (two), Nigeria (nine) and Senegal (three). Nine countries (56.3%) had no history of external beam radiotherapy (EBRT). The largest increase in absolute EBRT capacity occurred from 2017 to 2019, during which 13 MVMs were commissioned. The largest decrease in EBRT capacity occurred from 2015 to 2017, during which four LINACs and three COs were rendered non-operational. The ratio of million persons per MVM improved from 67.0 in 1979 to 17.8 in 2019. As of 2019, there was 0.09 MVM per 1000 cancer cases. CONCLUSIONS Western African nations have experienced an increase in the absolute number of MVMs and per capita radiotherapy capacity during the last 50 years, especially in the last decade. As non-functional LINACs contributed to a temporary decline in the EBRT infrastructure, dual use of CO/LINAC technologies may act to promote the availability of EBRT treatment in centres with capacity for multiple MVMs.

Background: First Nations, Inuit and Métis (FNIM) peoples in Canada exhibit high rates of cancer ... more Background: First Nations, Inuit and Métis (FNIM) peoples in Canada exhibit high rates of cancer mortality. Little information exists on access to radiation therapy (RT) among these populations. We sought to describe geographic access to RT, and to explore its relationship with cancer outcomes among regions inhabited by a higher proportion of FNIM peoples in Canada. Methods and Materials: We calculated the linear distance from the centroid of each Canadian health region to the nearest RT center using a geographic analytical techniques, and compared distance between regions with a higher (≥ 23%) vs lower (< 23%) proportion of FNIM peoples (self-identified as Aboriginals through census data from Statistics Canada). We examined relationships between distance and proportion of FNIM peoples on cancer outcomes in an initial exploratory analysis, using age-standardized all-cancer mortality-to-incidence ratios (MIRs) from 2010 to 2012. A prediction model based on recursive partitioning was created, and the resulting groups were compared using one-way analyses of variance and nonparametric tests. Results: Health regions inhabited by a higher proportion of FNIM peoples were located further from RT centers (799 vs 120 km, p < .0001), and had worse cancer outcomes (MIR 0.53 vs 0.42, p < .0001). Among a subset of overlapping regions 150-750 km from RT centers, those with a higher proportion of FNIM peoples had worse outcomes (MIR 0.50 vs 0.44, p = .03), despite a similar distance (p = .47). In our prediction model, distance to an RT center had the largest impact on MIR, followed equally by smoking and proportion of FNIM peoples. Regions closer to RT centers with a higher proportion of FNIM peoples had poor outcomes that did not differ from regions furthest away (p = .41), and showed a trend toward worse outcomes compared to regions with a lower proportion of FNIM peoples within the same distance (p = .07). Conclusions: Regions inhabited by a higher proportion of FNIM populations are further away from RT centers and have poorer outcomes. Distance is an important factor but does not completely explain these regions' poorer cancer outcomes.

Journal of Global Oncology, Oct 1, 2018

Aim and purpose: The session aims at outlining actions that the healthcare community can take to ... more Aim and purpose: The session aims at outlining actions that the healthcare community can take to improve the current situation and inform cervix cancer control plans. Highlighting the need to address opportunities in the prevention and management of cervix cancer, the session will provide guidance on primary, secondary and tertiary prevention and management of cervix cancer and will discuss the role of radiotherapy, while showcasing examples of collaboration. Audiences: Healthcare professionals with a special interest in…

Revista médica del Uruguay, 2004

Resumen Se analizaron 560 pacientes consecutivos con cáncer localizado de próstata tratados con r... more Resumen Se analizaron 560 pacientes consecutivos con cáncer localizado de próstata tratados con radioterapia conformal tridimensional entre 1993 y 2001. La sobrevida global actuarial a los nueve años fue de 71%, y la sobrevida causa específica de 88%. La mortalidad cruda por cáncer de próstata fue de 4,8% mientras que la mortalidad por otras causas fue de 8,3%. La sobrevida libre de recaída bioquímica en función del grupo de riesgo fue de 83%, 68% y 41% a los nueve años, respectivamente para los grupos de riesgo bajo, intermedio y alto en 504 pacientes (p<0,05). La dosis mayor o igual a 72 Gy mejora el control bioquímico a los siete años en todos los grupos de riesgo aunque sólo es estadísticamente significativa en el grupo de riesgo alto (p<0,006). El modelo de Cox reveló que solamente el grupo de riesgo, la dosis total como variable continua y el antígeno prostático específico inicial como variable categórica fueron significativos. Cuando el modelo de Cox fue aplicado a los 188 pacientes de riesgo alto, el uso de la hormonoterapia de inducción o concomitante, o ambas, y la edad, resultaron además significativos. La tasa actuarial de complicaciones severas a diez años grados 3 y 4 (no hubo complicaciones grado 5) fue de 1,2% para las urinarias y de 1,4% para las digestivas. La radioterapia conformal tridimensional a altas dosis es un tratamiento efectivo y de baja morbilidad para el tratamiento del cáncer localizado de próstata.

$Research paper thumbnail of Dose-fractionation sensitivities in radiotherapy of prostate cancers deduced from seven international institutional datasets$

Clinical Oncology, Apr 1, 2021

Aims: Childhood cancer survival is suboptimal in most low-and middle-income countries (LMICs). Ra... more Aims: Childhood cancer survival is suboptimal in most low-and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' Materials and methods: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. Results: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from highincome countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. Conclusions: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients.

Clinical Oncology, Feb 1, 2017

Clinical Oncology j o ur n a l h o m e p a ge : w w w. c l i n i c a l on c o l o gy o n l i ne. ... more Clinical Oncology j o ur n a l h o m e p a ge : w w w. c l i n i c a l on c o l o gy o n l i ne. n e t

International Journal of Radiation Oncology Biology Physics, Mar 1, 1999

Purpose: To compare results and complications of our previous low-dose-rate (LDR) brachytherapy s... more Purpose: To compare results and complications of our previous low-dose-rate (LDR) brachytherapy schedule for early-stage cancer of the cervix, with a prospectively designed medium-dose-rate (MDR) schedule, based on the linear-quadratic model (LQ). Methods and Materials: A combination of brachytherapy, external beam pelvic and parametrial irradiation was used in 102 consecutive Stage Ib-IIb LDR treated patients (1986-1990) and 42 equally staged MDR treated patients (1994-1996). The planned MDR schedule consisted of three insertions on three treatment days with six 8-Gy brachytherapy fractions to Point A, two on each treatment day with an interfraction interval of 6 hours, plus 18 Gy external whole pelvic dose, and followed by additional parametrial irradiation. The calculated biologically effective dose (BED) for tumor was 90 Gy 10 and for rectum below 125 Gy 3. Results: In practice the MDR brachytherapy schedule achieved a tumor BED of 86 Gy 10 and a rectal BED of 101 Gy 3. The latter was better than originally planned due to a reduction from 85% to 77% in the percentage of the mean dose to the rectum in relation to Point A. The mean overall treatment time was 10 days shorter for MDR in comparison with LDR. The 3-year actuarial central control for LDR and MDR was 97% and 98% (p ‫؍‬ NS), respectively. The Grades 2 and 3 late complications (scale 0 to 3) were 1% and 2.4%, respectively for LDR (3-year) and MDR (2-year). Conclusions: LQ is a reliable tool for designing new schedules with altered fractionation and dose rates. The MDR schedule has proven to be an equivalent treatment schedule compared with LDR, with an additional advantage of having a shorter overall treatment time. The mean rectal BED Gy 3 was lower than expected.

Clinical Oncology, Feb 1, 2015

International Journal of Radiation Oncology Biology Physics, 2012

Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fraction... more Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. Methods and Materials: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was used for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), a (dose-response slope using very low doses per fraction), and the ratio a/b that characterizes dose-fractionation sensitivity. Results: There was no significant difference between the a/b value for the three risk groups, and the value of a/b for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the a/b value. Conclusions: The overall a/b value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings.

DOAJ (DOAJ: Directory of Open Access Journals), Sep 1, 2006

This paper describes the biological mechanisms of normal tissue reactions after radiation therapy... more This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of increasing the size of the irradiated volume, early and late tissue reactions, effects of changes in dose fractionation and dose rate, and combined chemotherapy and radiotherapy responses. Examples are given of increases in knowledge of clinical radiobiology from trials of new protocols. Potential modification to treatments include the use of biological response modifiers. The introduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;response prediction&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; modifications to treatments might also be available in the near future. Finally, the paper points out that in some radiotherapy centers, the biologically-effective doses prescribed for combined brachytherapy and teletherapy treatment of cervix cancer are lower than those prescribed in other centers. This issue needs to be addressed further. The wealth of preclinical and clinical data has led to a much greater understanding of the biological basis to radiotherapy. This understanding has underpinned a variety of new approaches in radiotherapy, including both physical and biological strategies. There is also the important issue of treatment of a large number of cancers in developing countries, for which efficacious resource-sparing protocols are being continuously developed. A unified scoring system should be widely accepted as the new standard in reporting the adverse effects of radiation therapy. Likewise, late toxicity should be reported on an actuarial basis as a mandatory endpoint.

Radiotherapy and Oncology, May 1, 2012

Creative Education, 2017

that the changes which are introduced can remain sustainable within the context of national healt... more that the changes which are introduced can remain sustainable within the context of national healthcare, education and political systems.

Radiotherapy and Oncology, Apr 1, 2014

To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combi... more To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combined external beam and high-dose-rate brachytherapy, in comparison with expected results using projections based on dose/fractionation/response parameter values deduced from a previous external-beam-alone 5969-patient multicentre dataset. Results on a total of 3145 prostate cancer patients receiving brachytherapy (BT) as part or all of their treatment were collected from 10 institutions, and subjected to linear-quadratic (LQ) modelling of dose response and fractionation parameters. Treatments with BT components of less than 25Gy, 3-4 BT fractions, doses per BT fraction up to 6Gy, and treatment times of 3-7weeks, all gave outcomes expected from LQ projections of the external-beam-alone data (α/β=1.42Gy). However, BT doses higher than 30Gy, 1-2 fractions, 9 fractions (BT alone), doses per fraction of 9-15Gy, and treatment in only 1week (one example), gave local control levels lower than the expected levels by up to ∼35%. There are various potential causes of the lower-than-projected control levels for some schedules of brachytherapy: it seems plausible that cold spots in the brachytherapy dose distribution may be contributory, and the applicability of the LQ model at high doses per fraction remains somewhat uncertain. The results of further trials may help elucidate the true benefit of hypofractionated high-dose-rate brachytherapy.

$Research paper thumbnail of Feasibility of concomitant cisplatin with hypofractionated radiotherapy for locally advanced head and neck squamous cell carcinoma$

BMC Cancer, Oct 23, 2018

Background: The evolution of radiotherapy over recent decades has reintroduced the hypofractionat... more Background: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumor sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). Methods: This single-arm trial was designed to evaluate the safety and feasibility of HYP-RT with concomitant CDDP in LAHNC. Stage III and IV patients withnonmetastatic disease were enrolled. Patients were submitted to intensity modulatedradiation therapy, which comprised 55 Gy/20 fractions to the gross tumor and44-48 Gy/20 fractions to the areas of subclinical disease. Concomitant CDDPconsisted of 4 weekly cycles of 35 mg/m2. The primary endpoints were the treatment completion rate and acute toxicity. Results: Twenty patients were enrolled from January 2015 to September 2016, and 12 (60%) were classified as unresectable. All patients completed the total dose of radiotherapy, and 19 patients (95%) received at least 3 of 4 cycles of chemotherapy. The median overall treatment time was 29 days (27-34). Grade 4 toxicity was reported twice (1 fatigue and 1 lymphopenia). The rates of grade 3 dermatitis and mucositis were 30% and 40%, respectively, with spontaneous resolution. Nasogastric tubes were offered to 15 patients (75%) during treatment; 4 patients (20%) needed feeding tubes after 2 months, and only 1 patient needed a feeding tube after 12 months. Conclusion: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted.

Lancet Oncology, Jul 1, 2019

Background-Radiotherapy is standard of care for cervical cancer, but major global gaps in access ... more Background-Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination.