Publications by authors named "Luca Incrocci"

123 Publications

High-dose Radiotherapy or Androgen Deprivation Therapy (HEAT) as Treatment Intensification for Localized Prostate Cancer: An Individual Patient-data Network Meta-analysis from the MARCAP Consortium.

Eur Urol 2022 Apr 22. Epub 2022 Apr 22.

Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: The relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown.

Objective: To perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT.

Design, Setting, And Participants: An NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11862 patients. Patients received one of the six permutations of low-dose RT (64 to <74 Gy) ± STADT or LTADT, high-dose RT (≥74 Gy), or high-dose RT ± STADT or LTADT.

Outcome Measurements And Statistical Analyses: Metastasis-free survival (MFS) was the primary endpoint. Frequentist and Bayesian NMAs were performed to rank the various treatment strategies by MFS and biochemical recurrence-free survival (BCRFS).

Results And Limitations: Median follow-up was 8.8 yr (interquartile range 5.7-11.5). The greatest relative improvement in outcomes was seen for addition of LTADT, irrespective of RT dose, followed by addition of STADT, irrespective of RT dose. RT dose escalation did not improve MFS either in the absence of ADT (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.80-1.18) or with STADT (HR 0.99, 95% CI 0.8-1.23) or LTADT (HR 0.94, 95% CI 0.65-1.37). According to P-score ranking and rankogram analysis, high-dose RT + LTADT was the optimal treatment strategy for both BCRFS and longer-term outcomes.

Conclusions: Conventionally escalated RT up to 79.2 Gy, alone or in the presence of ADT, does not improve MFS, while addition of STADT or LTADT to RT alone, regardless of RT dose, consistently improves MFS. RT dose escalation does provide a high probability of improving BCRFS and, provided it can be delivered without compromising quality of life, may represent the optimal treatment strategy when used in conjunction with ADT.

Patient Summary: Using a higher radiotherapy dose when treating prostate cancer does not reduce the chance of developing metastases or death, but it does reduce the chance of having a rise in prostate-specific antigen (PSA) signifying recurrence of cancer. Androgen deprivation therapy improves all outcomes. A safe increase in radiotherapy dose in conjunction with androgen deprivation therapy may be the optimal treatment.
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http://dx.doi.org/10.1016/j.eururo.2022.04.003DOI Listing
April 2022

Impact of the COVID-19 outbreak on prostate cancer care in the Netherlands.

Cancer Treat Res Commun 2022 2;31:100553. Epub 2022 Apr 2.

Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, DT 3511 Netherlands; Radboud Institute for Health Sciences, Radboud university medical centre, Nijmegen, GA 6525 Netherlands. Electronic address:

Introduction: The COVID-19 outbreak has affected care for non-COVID diseases like cancer. We evaluated the impact of the COVID-19 outbreak on prostate cancer care in the Netherlands.

Methods: Prostate cancer diagnoses per month in 2020-2021 versus 2018-2019 were compared based on preliminary data of the Netherlands Cancer Registry (NCR) and nationwide pathology network. Detailed data was retrieved from the NCR for the cohorts diagnosed from March-May 2020 (first COVID-19 wave) and March-May 2018-2019 (reference). Changes in number of diagnoses, age, disease stage and first-line treatment were compared.

Results: An initial decline of 17% in prostate cancer diagnoses during the first COVID-19 wave was observed. From May onwards the number of diagnoses started to restore to approximately 95% of the expected number by the end of 2020. Stage at diagnosis remainedstable over time. In low-risk localised prostate cancer radical prostatectomy was conducted more often in week 9-12 (21% versus 12% in the reference period; OR=1.9, 95% CI; 1.2-3.1) and less active surveillance was applied (67% versus 78%; OR=0.6, 95% CI; 0.4-0.9). In the intermediate-risk group, a similar change was observed in week 13-16. Radical prostatectomy volumes in 2020 were comparable to 2018-2019.

Conclusion: During the first COVID-19 wave the number of prostate cancer diagnoses declined. In the second half of 2020 this largely restored although the number remained lower than expected. Changes in treatment were temporary and compliant with adapted guidelines. Although delayed diagnoses could result in a less favourable stage distribution, possibly affecting survival, this seems not very likely.
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http://dx.doi.org/10.1016/j.ctarc.2022.100553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975755PMC
May 2022

Seminal vesicle inter- and intra-fraction motion during radiotherapy for prostate cancer: A review.

Radiother Oncol 2022 Apr 11;169:15-24. Epub 2022 Feb 11.

Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, Rotterdam, Netherlands.

A review of studies on seminal vesicle motion was performed to improve the understanding of these treatment uncertainties. This will aid planning target volume margin reduction, which is necessary for hypofractionation of high-risk prostate cancer. Embase, Medline, Web of science Core collection, Cochrane CENTRAL register of trials and Google scholar were searched for publications including 3D information on seminal vesicle motion. In total 646 publications were found of which 22 publications were eligible for inclusion. The mean, systematic and random error of inter- and intra-fraction translations are reported, as well as rotations. The translations of the seminal vesicles is smallest in the left-right direction, whereas the rotation was largest around this axis. Although rectal and bladder filling status were the main cause for seminal vesicle motion, no apparent effect on magnitude of motion was seen when different bladder and rectal preparation protocols were used. Inter- and intra-fraction motion of the seminal vesicles is significant. In the studies, systematic and random errors range between 1-7 mm and 1-5 mm respectively, and are largely uncorrelated to prostate motion. The maximum correlation between seminal vesicle and prostate motion was reported with an R of 0.7, while 3 other studies report lower and/or non-significant correlations. Five studies report a planning target volume margin of approximately 8 mm. This margin is in line with the results of four relevant dosimetric studies. Mitigating the inter- and intra-fraction motion of the seminal vesicles, including prostate tracking, has the potential to reduce planning target volume margins.
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http://dx.doi.org/10.1016/j.radonc.2022.02.002DOI Listing
April 2022

Sexual problems in patients with hematological diseases: a systematic literature review.

Support Care Cancer 2022 Jun 21;30(6):4603-4616. Epub 2022 Jan 21.

Cancer Center Amsterdam (CCA), Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands.

Purpose: Sexual problems are frequently reported by recipients of hematopoietic stem cell transplantation (HCT). However, little is known about the impact of hematological malignancies and their treatments, without HCT being a part of the treatment regimen. The goal of this systematic review was to examine the prevalence of various sexual problems among patients treated for hematological malignancies without HCT.

Methods: The work focused on online databases available from their inception until 11 November 2020. The data related to sexuality in adult patients diagnosed with hematological malignancies. Selected studies were appraised for methodological quality.

Results: Twenty-four studies were included. Twenty-two studies were observational cross-sectional cohort studies, and two studies had a prospective longitudinal design; fourteen studies used non-validated instruments; only two studies used the multidimensional concept of sexuality; six studies compared sexual problems in the target population with reference data. Based on the few high-quality studies, sexual problems occurred in 18-50% of acute leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma patients.

Conclusion: Understanding sexual problems in patients treated for hematological malignancies without HCT is not only hampered by the variability in methodology, but also by the lack of research on patients using novel therapies. The exact impact of the diagnosis and treatment of a hematological malignancy on sexual function remains to be answered. Longitudinal studies focusing on the effects of the diagnosis and treatment of hematological malignancies on sexuality using validated questionnaires and comparison with normative data are hugely needed.
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http://dx.doi.org/10.1007/s00520-021-06731-7DOI Listing
June 2022

Practical Guidelines on Implementing Hypofractionated Radiotherapy for Prostate Cancer in Africa.

Front Oncol 2021 1;11:725103. Epub 2021 Dec 1.

Department of Radiotherapy, Erasmus Medical Center (MC), Rotterdam, Netherlands.

Among a growing body of literature in global oncology, several articles project increased cost savings and radiotherapy access by adopting hypofractionated radiotherapy (HFRT) in low- and middle-income countries (LMICs) like those in Africa. Clinical trials in Europe and the USA have demonstrated HFRT to be non-inferior to conventional radiotherapy for eligible patients with several cancers, including prostate cancer. This could be a highly recommended option to battle a severely large and growing cancer burden in resource-limited regions. However, a level of implementation research may be needed in limited resource-settings like in Africa. In this article, we present a list of evidence-based recommendations to practice HFRT on eligible prostate cancer patients. As literature on HFRT is still developing, these guidelines were compiled from review of several clinical trials and professionally accredited material with minimal resource requirements in mind. HFRT guidelines presented here include patient eligibility, prescription dose schedules, treatment planning and delivery techniques, and quality assurance procedures. The article provides recommendations for both moderately hypofractionated (2.4-3.4Gy per fraction) and ultrahypofractionated (5Gy or more per fraction) radiation therapy when administered by 3D-Conformal Radiotherapy, Intensity Modulated Radiation Therapy, or Image-Guided Radiotherapy. In each case radiation oncology health professionals must make the ultimate judgment to ensure safety as more LMIC centers adopt HFRT to combat the growing scourge of cancer.
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http://dx.doi.org/10.3389/fonc.2021.725103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673781PMC
December 2021

Impact of Advanced Radiotherapy on Second Primary Cancer Risk in Prostate Cancer Survivors: A Nationwide Cohort Study.

Front Oncol 2021 26;11:771956. Epub 2021 Nov 26.

Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands.

Purpose: External Beam Radiotherapy (EBRT) techniques dramatically changed over the years. This may have affected the risk of radiation-induced second primary cancers (SPC), due to increased irradiated low dose volumes and scatter radiation. We investigated whether patterns of SPC after EBRT have changed over the years in prostate cancer (PCa) survivors.

Materials And Methods: PCa survivors diagnosed between 1990-2014 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were divided in three time periods, representing 2-dimensional Radiotherapy (RT), 3-dimensional conformal RT (3D-CRT), and the advanced RT (AdvRT) era. Standardized incidence ratios (SIR) and absolute excess risks (AER) were calculated to estimate relative and excess absolute SPC risks. Sub-hazard ratios (sHRs) were calculated to compare SPC rates between the EBRT and prostatectomy cohort. SPCs were categorized by subsite and anatomic region.

Results: PCa survivors who received EBRT had an increased risk of developing a solid SPC (SIR=1.08; 1.05-1.11), especially in patients aged <70 years (SIR=1.13; 1.09-1.16). Pelvic SPC risks were increased (SIR=1.28; 1.23-1.34), with no obvious differences between the three EBRT eras. Non-pelvic SPC were only significantly increased in the AdvRT era (SIR=1.08; 1.02-1.14), in particular for the 1-5 year follow-up period. Comparing the EBRT cohort to the prostatectomy cohort, again an increased pelvic SPC risk was found for all EBRT periods (sHRs= 1.61, 1.47-1.76). Increased non-pelvic SPC risks were present for all RT eras and highest for the AdvRT period (sHRs=1.17, 1.06-1.29).

Conclusion: SPC risk in patients with EBRT is increased and remained throughout the different EBRT eras. The risk of developing a SPC outside the pelvic area changed unfavorably in the AdvRT era. Prolonged follow-up is needed to confirm this observation. Whether this is associated with increased irradiated low-dose volumes and scatter, or other changes in clinical EBRT practice, is the subject of further research.
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http://dx.doi.org/10.3389/fonc.2021.771956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662556PMC
November 2021

Patient-Reported Outcomes in the Acute Phase of the Randomized Hypofractionated Irradiation for Prostate Cancer (HYPRO) Trial.

Int J Radiat Oncol Biol Phys 2022 03 3;112(4):870-879. Epub 2021 Nov 3.

Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Purpose: Many patients experience bowel and bladder toxicity during the acute phase of radiation therapy for prostate cancer. Recent literature indicates that hypofractionation (HF) might increase this acute response but little is known on patient-reported outcome during this phase with HF. We evaluated the course of patient-reported acute symptoms during HF versus standard fractionated (SF) radiation therapy within the hypofractionated irradiation for prostate cancer (HYPRO) trial.

Methods And Materials: In the HYPRO trial patients were treated with either 64.4 Gy (HF) in 19 fractions (3 times per week) or 78 Gy (SF) in 39 fractions (5 times per week). Normalized total dose for 2 Gy/fractions (NTD)for acute toxicity (α/β ratio of 10) for HF was 72.1 Gy with a similar dose rate of 10.2 Gy per week. Among the 794 patients who were previously eligible for acute grade ≥2 toxicity assessment, 717 had filled out ≥1 symptom questionnaires. For each maximum symptom, we scored "any complaint" and "moderate-severe complaint." Differences were tested by χ test, and associations with clinical factors were tested using logistic regression. Significance was set at P ≤ .008 to adjust for multiple testing.

Results: We observed significantly higher rates of moderate-severe painful defecation (HF 10.8%, SF 5.3%), any mucus discharge (HF 47.1%, SF 37.4%), any rectal blood loss (HF 16.1%, SF 9.3%), increased daily stool frequency ≥4 and ≥6 (HF 34.6%/13.8%, SF 25.6%/7.0%), and any urinary straining (HF 69.9%, SF 58.0%). At 3 months postradiation therapy, rates dropped considerably with similar levels for HF and SF. Hormonal treatment was associated with less acute gastrointestinal symptoms.

Conclusion: The increased patient-reported acute rectal symptoms with HF confirmed the previously reported results on acute grade ≥2 rectal toxicity. The increase in bladder symptoms with HF was not identified previously. These observations contradict the NTD calculations. We observed no patterns of persisting complaints with HF after the acute period; therefore, HF is well tolerated and only associated with a temporary increase of symptoms.
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http://dx.doi.org/10.1016/j.ijrobp.2021.10.139DOI Listing
March 2022

Copper Tolerance and Accumulation on L'Hér. Grown in Hydroponic Culture.

Plants (Basel) 2021 Aug 12;10(8). Epub 2021 Aug 12.

Department of Agricultural Sciences, Biotechnology and Food Science, Cyprus University of Technology, Limassol 3603, Cyprus.

Heavy metal contamination is a major health issue concerning the commercial production of medicinal and aromatic plants (MAPs) that are used for the extraction of bioactive molecules. Copper (Cu) is an anthropogenic contaminant that, at toxic levels, can accumulate in plant tissues, affecting plant growth and development. On the other hand, plant response to metal-induced stress may involve the synthesis and accumulation of beneficial secondary metabolites. In this study, hydroponically grown plants were exposed to different Cu concentrations in a nutrient solution (4, 25, 50, 100 μM) to evaluate the effects Cu toxicity on plant growth, mineral uptake and distribution in plants, some stress indicators, and the accumulation of bioactive secondary metabolites in leaf tissues. resulted in moderately tolerant Cu toxicity. At Cu concentrations up to 100 μM, biomass production was preserved and was accompanied by an increase in phenolics and antioxidant capacity. The metal contaminant was accumulated mainly in the roots. The leaf tissues of Cu-treated may be safely used for the extraction of bioactive molecules.
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http://dx.doi.org/10.3390/plants10081663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398543PMC
August 2021

Association between incidental dose outside the prostate and tumor control after modern image-guided radiotherapy.

Phys Imaging Radiat Oncol 2021 Jan 5;17:25-31. Epub 2021 Jan 5.

Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands.

Background And Purpose: External beam radiotherapy for prostate cancer deposits incidental dose to a region surrounding the target volume. Previously, an association was identified between tumor control and incidental dose for patients treated with conventional radiotherapy. We investigated whether such an association exists for patients treated using intensity modulated radiotherapy (IMRT) and tighter margins.

Materials And Methods: Computed tomography scans and three-dimensional treatment planning dose distributions were available from the Dutch randomized HYPRO trial for 397 patients in the standard fractionation arm (39 × 2 Gy) and 407 patients in the hypofractionation arm (19 × 3.4 Gy), mainly delivered using online image-guided IMRT. Endpoint was any treatment failure within 5 years. A mapping of 3D dose distributions between anatomies was performed based on distance to the surface of the prostate delineation. Mean mapped dose distributions were computed for patient groups with and without failure, obtaining dose difference distributions. Random patient permutations were performed to derive p values and to identify relevant regions.

Results: For high-risk patients treated in the conventional arm, higher incidental dose was significantly associated with a higher probability of tumor control in both univariate and multivariate analysis. The locations of the excess dose mainly overlapped with the position of obturator internus muscles at about 2.5 cm from the prostate surface. No such relationship could be established for intermediate-risk patients.

Conclusions: An association was established between reduced treatment failure and the delivery of incidental dose outside the prostate for high-risk patients treated using conventionally fractionated IMRT.
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http://dx.doi.org/10.1016/j.phro.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057954PMC
January 2021

Impact of COVID-19 on Cancer Care Delivery in Africa: A Cross-Sectional Survey of Oncology Providers in Africa.

JCO Glob Oncol 2021 03;7:368-377

National Center for Radiotherapy and Nuclear Medicine, Korle-Bu Teaching Hospital, Accra, Ghana.

Purpose: The COVID-19 pandemic has disrupted cancer care globally. There are limited data of its impact in Africa. This study aims to characterize COVID-19 response strategies and impact of COVID-19 on cancer care and explore misconceptions in Africa.

Methods: We conducted a web-based cross-sectional survey of oncology providers in Africa between June and August 2020. Descriptive statistics and comparative analysis by income groups were performed.

Results: One hundred twenty-two participants initiated the survey, of which 79 respondents from 18 African countries contributed data. Ninety-four percent (66 of 70) reported country mitigation and suppression strategies, similar across income groups. Unique strategies included courier service and drones for delivery of cancer medications (9 of 70 and 6 of 70, respectively). Most cancer centers remained open, but > 75% providers reported a decrease in patient volume. Not previously reported is the fear of infectivity leading to staff shortages and decrease in patient volumes. Approximately one third reported modifications of all cancer treatment modalities, resulting in treatment delays. A majority of participants reported ≤ 25 confirmed cases (44 of 68, 64%) and ≤ 5 deaths because of COVID-19 (26 of 45, 58%) among patients with cancer. Common misconceptions were that Africans were less susceptible to the virus (53 of 70, 75.7%) and decreased transmission of the virus in the African heat (44 of 70, 62.9%).

Conclusion: Few COVID-19 cases and deaths were reported among patients with cancer. However, disruptions and delays in cancer care because of the pandemic were noted. The pandemic has inspired tailored innovative solutions in clinical care delivery for patients with cancer, which may serve as a blueprint for expanding care and preparing for future pandemics. Ongoing public education should address COVID-19 misconceptions. The results may not be generalizable to the entire African continent because of the small sample size.
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http://dx.doi.org/10.1200/GO.20.00569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081536PMC
March 2021

Hypofractionated Radiotherapy in African Cancer Centers.

Front Oncol 2020 19;10:618641. Epub 2021 Feb 19.

Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, United States.

In the advent of the coronavirus disease (COVID-19) pandemic, professional societies including the American Society for Radiation Oncology and the National Comprehensive Cancer Network recommended adopting evidence-based hypofractionated radiotherapy (HFRT). HFRT benefits include reduction in the number of clinical visits for each patient, minimizing potential exposure, and reducing stress on the limited workforce, especially in resource-limited settings as in Low-and-Middle-Income Countries (LMICs). Recent studies for LMICs in Africa have also shown that adopting HFRT can lead to significant cost reductions and increased access to radiotherapy. We assessed the readiness of 18 clinics in African LMICs to adopting HFRT. An IRB-approved survey was conducted at 18 RT clinics across 8 African countries. The survey requested information regarding the clinic's existing equipment and human infrastructure and current practices. Amongst the surveyed clinics, all reported to already practicing HFRT, but only 44% of participating clinics reported adopting HFRT as a common practice. Additionally, most participating clinical staff reported to have received formal training appropriate for their role. However, the survey data on treatment planning and other experience with contouring highlighted need for additional training for radiation oncologists. Although the surveyed clinics in African LMICs are familiar with HFRT, there is need for additional investment in infrastructure and training as well as better education of oncology leaders on the benefits of increased adoption of evidence-based HFRT during and beyond the COVID-19 era.
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http://dx.doi.org/10.3389/fonc.2020.618641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933544PMC
February 2021

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

Front Oncol 2020 13;10:605119. Epub 2020 Nov 13.

Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, Netherlands.

Purpose: Concerns have been raised that modern intensity modulated radiotherapy (IMRT) may be associated with increased second primary cancer risks (SPC) compared to previous three-dimensional conformal radiation techniques (3DCRT), due to increased low dose volumes and more out-of-field ionizing dose to peripheral tissue further away from the target. We assessed the impact of treatment technique on SPC risks in a cohort of prostate cancer (PCa) survivors.

Material And Methods: The study cohort comprised 1,561 PCa survivors aged 50-79 years at time of radiotherapy, treated between 2006-2013 (N=707 IMRT, N=854 3DCRT). Treatment details were extracted from radiotherapy systems and merged with longitudinal data of the Netherlands Cancer Registry to identify SPCs. Primary endpoint was the development of a solid SPC (excluding skin cancer) in peripheral anatomical regions, i.e. non-pelvic. Applied latency period was 12 months. SPC rates in the IMRT cohort (total cohort and age subgroups) were compared to 1) the 3DCRT cohort by calculating Sub-Hazard Ratios (sHR) using a competing risk model, and 2) to the general male population by calculating Standardized Incidence Ratios (SIR). Models were adjusted for calendar period and age.

Results: Median follow-up was 8.0 years (accumulated 11,664 person-years at-risk) with 159 cases developing ≥1 non-pelvic SPC. For IMRT vs 3DCRT we observed a significantly (=0.03) increased risk (sHR=1.56, 95% Confidence Interval (CI) 1.03-2.36, corresponding estimated excess absolute risk (EAR) of +7 cases per 10,000 person-years). At explorative analysis, IMRT was in particular associated with increased risks within the subgroup of active smokers (sHR 2.94, =0.01). Within the age subgroups 50-69 and 70-79 years, the sHR for non-pelvic SPC was 3.27 (=0.001) and 0.96 (=0.9), respectively. For pelvic SPC no increase was observed (sHR=0.8, 0.4). Compared to the general population, IMRT was associated with significantly increased risks for non-pelvic SPC in the 50-69 year age group (SIR=1.90, <0.05) but not in the 70-79 years group (SIR=1.08).

Conclusion: IMRT is associated with increased SPC risks for subjects who are relatively young at time of treatment. Additional research on aspects of IMRT that may cause this effect is essential to minimize risks for future patients receiving modern radiotherapy.
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http://dx.doi.org/10.3389/fonc.2020.605119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691574PMC
November 2020

Evaluation of Major Minerals and Trace Elements in Wild and Domesticated Edible Herbs Traditionally Used in the Mediterranean Area.

Biol Trace Elem Res 2021 Sep 5;199(9):3553-3561. Epub 2020 Nov 5.

Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.

The human diet is characterized by the intake of major minerals (Na, K, Ca, Mg, P, N) and trace elements (Zn, Mn, Se, Cu, Fe, Co, I, Cr, F, Pb, Cd) for their key role in many metabolic functions. Nowadays, the research of sources able to improve their intake is in continuous evolution, especially in the undeveloped countries. In this sense, wild edible herbs, commonly used since ancient times, can represent a good alternative to improve the daily human intake of minerals. In this study, four wild edible species, Rumex acetosa, Picris hieracioides, Cichorium intybus, and Plantago coronopus, were analyzed for their content in Na, K, Ca, Mg, Cu, Mn, Fe, and Zn and, besides, three domestications (named "soilless," pot, and open field) were evaluated in the analyzed species in the prospective of their commercialization as valuable sources of minerals in the human diet. Nitrate and oxalate contents were also evaluated, given their negative impact on human health. Results unveil that open field domestication allowed the plants to maintain the content of major minerals similar to those measured in wild plants, especially in C. intybus and P. hieracioides. The trace elements Cu, Mn, Fe, and Zn were not recorded at high content irrespectively to the wild collection or domestications. Finally, plants grown in the open field also accounted for a high oxalate and nitrate content, especially in R. acetosa. Further researches should be aimed at decreasing the oxalate and nitrate content in the domesticated species and to promote the commercialization of the domesticated species.
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http://dx.doi.org/10.1007/s12011-020-02467-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257512PMC
September 2021

Radiotherapy Practice for Treatment of Bone Metastasis in Ethiopia.

JCO Glob Oncol 2020 09;6:1422-1427

Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.

Purose: Ethiopia has one cobalt radiotherapy (RT) machine to serve a population of more than 100 million. The purpose of this study was to report on patterns of palliative RT of bone metastasis in a severely low-capacity setting.

Patients And Methods: Patient and treatment characteristics of patients irradiated for palliation of symptomatic bone metastasis were extracted from a retrospective database of patients treated between May 2015 and January 2018. This database included a random sample of 1,823 of the estimated 4,000 patients who were treated with RT within in the study period. Associations between the applied RT schedule and patient and tumor characteristics were evaluated with the χ test. Hypothetical savings of RT sessions and time were compared in the case of a single-fraction policy.

Results: From the database, 234 patients (13%) were treated for bone metastasis. Most patients were ≤ 65 years of age (n = 189; 80%) and female (n = 125; 53%). The most common primary sites were breast (n = 82; 35%) and prostate (n = 36; 15%). Fractionated regimens were preferred over single fraction: 20 Gy in 5 fractions (n = 192; 82.1%), 30 Gy in 10 fractions (n = 7; 3%), and 8 Gy in 1 fraction (n = 28; 12%). Factors associated with single-fraction RT included nonaxial sites of bone metastasis ( < .01) and an address outside Addis Ababa ( ≤ .01). If single-fraction RT would have been given uniformly for bone metastasis, this would have resulted in a 78% reduction in the number of RT sessions and 76% reduction in total RT time.

Conclusion: The pattern of palliative RT for bone metastasis in Ethiopia favors fractionated regimens over single fraction. Efforts should be made to adopt evidence-based and cost-effective guidelines.
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http://dx.doi.org/10.1200/GO.20.00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529534PMC
September 2020

Comparison of Three Domestications and Wild-Harvested Plants for Nutraceutical Properties and Sensory Profiles in Five Wild Edible Herbs: Is Domestication Possible?

Foods 2020 Aug 6;9(8). Epub 2020 Aug 6.

Department of Agriculture, Food and Environment, University of Pisa, 56124 Pisa, Italy.

In this study, five wild edible herbs traditionally consumed in the Tuscany region (Italy) were evaluated for their potential in human nutrition. The nutraceutical characterization of , , , , and , as well as their sensory profile were reported. Additionally, a preliminary assessment of completely different domestication of the wild species (named "soilless", pot, and open field) was conducted to verify the possibility of their marketability, which is impossible if the plants are only gathered as wild. The open field domestication allowed to obtain plants with nutraceutical and sensory profiles similar to those of the wild species, especially in , , and The pot domestication allow to obtain plants with chlorophyll and carotenoid contents close to those of the wild species, as well as a lower total phenolic and flavonoid content and ascorbic acid content than wild species. In the "soilless" method, and exhibited a high quality in terms of phytochemicals and antioxidant activity. Afterward, the sensory profile was strongly affected by the domestication in terms of the palatability, except for and , which displayed Hedonic Index (HI) values close to the consumer acceptability limit (HI = 6). A sensory profile similar to that of wild species was reported in open field domestication, whereas a worse sensory profile was reported in and domesticated using the soilless method. Finally, according to the preliminary assessment carried out in this study through an analysis of the general nutraceutical properties, was shown to be the most promising species thanks to its intrinsically highest nutraceutical properties considering the marketability of wild edible herbs as "new" functional food. However, further research on the bioavailability and bioactivity tests of nutraceutical compounds present in this species are required to confirm the findings of this study.
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http://dx.doi.org/10.3390/foods9081065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466383PMC
August 2020

Automated Radiotherapy Planning for Patient-Specific Exploration of the Trade-Off Between Tumor Dose Coverage and Predicted Radiation-Induced Toxicity-A Proof of Principle Study for Prostate Cancer.

Front Oncol 2020 30;10:943. Epub 2020 Jun 30.

Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.

Currently, radiation-oncologists generally evaluate a single treatment plan for each patient that is possibly adapted by the planner prior to final approval. There is no systematic exploration of patient-specific trade-offs between planning aims, using a set of treatment plans with a-priori defined (slightly) different balances. To this purpose, we developed an automated workflow and explored its use for prostate cancer. For each of the 50 study patients, seven plans were generated, including the so-called clinical plan, with currently clinically desired ≥99% dose coverage for the low-dose planning target volume (PTV). The six other plans were generated with different, reduced levels of PTV coverage, aiming at reductions in rectum dose and consequently in predicted grade≥2 late gastro-intestinal (GI) normal tissue complication probabilities (NTCPs), while keeping other dosimetric differences small. The applied NTCP model included diabetes as a non-dosimetric predictor. All plans were generated with a clinically applied, in-house developed algorithm for automated multi-criterial plan generation. With diabetes, the average NTCP reduced from 24.9 ± 4.5% for ≥99% PTV coverage to 17.3 ± 2.6% for 90%, approaching the NTCP (15.4 ± 3.0%) without diabetes and full PTV coverage. Apart from intended differences in PTV coverage and rectum dose, other differences between the clinical plan and the six alternatives were indeed minor. Obtained NTCP reductions were highly patient-specific (ranging from 14.4 to 0.1%), depending on patient anatomy. Even for patients with equal NTCPs in the clinical plan, large differences were found in NTCP reductions. A clinically feasible workflow has been proposed for systematic exploration of patient-specific trade-offs between various treatment aims. For each patient, automated planning is used to generate a limited set of treatment plans with well-defined variations in the balances between the aims. For prostate cancer, trade-offs between PTV coverage and predicted GI NTCP were explored. With relatively small coverage reductions, significant NTCP reductions could be obtained, strongly depending on patient anatomy. Coverage reductions could also make up for enhanced NTCPs related to diabetes as co-morbidity, again dependent on the patient. The proposed system can play an important role in further personalization of patient care.
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http://dx.doi.org/10.3389/fonc.2020.00943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339044PMC
June 2020

Reply to: "Discussing sexuality in cancer care: towards personalized information for cancer patients and survivors".

Support Care Cancer 2021 02 15;29(2):535-537. Epub 2020 Jul 15.

Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, Netherlands.

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http://dx.doi.org/10.1007/s00520-020-05625-4DOI Listing
February 2021

Bayesian Sigmoid-Type Time Series Forecasting with Missing Data for Greenhouse Crops.

Sensors (Basel) 2020 Jun 7;20(11). Epub 2020 Jun 7.

Department of Computer Science, University of Pisa, 56127 Pisa, Italy.

This paper follows an integrated approach of Internet of Things based sensing and machine learning for crop growth prediction in agriculture. A Dynamic Bayesian Network (DBN) relates crop growth associated measurement data to environmental control data via hidden states. The measurement data, having (non-linear) sigmoid-type dynamics, are instances of the two classes observed and missing, respectively. Considering that the time series of the logistic sigmoid function is the solution to a reciprocal linear dynamic model, the exact expectation-maximization algorithm can be applied to infer the hidden states and to learn the parameters of the model. At iterative convergence, the parameter estimates are then used to derive a predictor of the measurement data several days ahead. To evaluate the performance of the proposed DBN, we followed three cultivation cycles of micro-tomatoes (MicroTom) in a mini-greenhouse. The environmental parameters were temperature, converted into Growing Degree Days (GDD), and the solar irradiance, both at a daily granularity. The measurement data were Leaf Area Index (LAI) and Evapotranspiration (ET). Although measurement data were only available scarcely, it turned out that high quality measurement data predictions were possible up to three weeks ahead.
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http://dx.doi.org/10.3390/s20113246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309099PMC
June 2020

Self-Reported Sexual Function in Sexually Active Male Hodgkin Lymphoma Survivors.

Sex Med 2020 Sep 2;8(3):428-435. Epub 2020 Jun 2.

Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Introduction: Unambiguous data on sexual dysfunction after Hodgkin lymphoma (HL) treatment are scarce.

Aims: To form a baseline in this area, we compared patient-reported sexual function in sexually active male HL survivors in complete remission with a sexually active, age-matched, male Dutch sample population. Furthermore, we explored whether sociodemographic and clinical factors were associated with sexual dysfunction in HL survivors and investigated whether reporting to perceive sexual problems was indicative for sexual dysfunction.

Methods: This cross-sectional study included male patients with HL who were treated with chemotherapy and age-matched sexually active males.

Main Outcome Measures: Outcome measures included the internationally validated International Index of Erectile Function (IIEF) and self-reported sexual problems by adding 3 items to the study-specific questionnaire.

Results: Erectile dysfunction (ED) occurred in 23.3% of the HL survivors vs in 23.0% of controls: respectively 13.3% and 12.3% had moderate to severe ED. However, more HL survivors positively answered the question whether they did perceive sexual problems than controls (20.0% vs 7.0%; P = .087). More patients treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procabazine, and prednisone (BEACOPP) had sexual problems 33.3% vs 8.3% who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (P = .057). Importantly, we found that the mean IIEF score for erectile function was 15.7 in HL survivors who reported to perceive sexual problems (moderate ED) vs 28.3 (normal) in those without perceiving sexual problems.

Conclusion: In general, sexual function of male HL survivors is comparable to that of matched normal controls. Perceiving sexual problems was associated with lower sexual function measured by the IIEF. None of the HL survivors who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine perceived sexual problems. However, one-third of HL survivors who were treated with BEACOPP did, including ED in one-third of the cases. This is an important consideration for daily clinical practice as BEACOPP is increasingly used as standard therapy in advanced-stage HL. Eeltink CM, Lissenberg-Witte BI, Incrocci L, et al. Self-Reported Sexual Function in Sexually Active Male Hodgkin Lymphoma Survivors. Sex Med 2020;8:428-435.
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http://dx.doi.org/10.1016/j.esxm.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471085PMC
September 2020

Local Dose Effects for Late Gastrointestinal Toxicity After Hypofractionated and Conventionally Fractionated Modern Radiotherapy for Prostate Cancer in the HYPRO Trial.

Front Oncol 2020 3;10:469. Epub 2020 Apr 3.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands.

Late gastrointestinal (GI) toxicity after radiotherapy for prostate cancer may have significant impact on the cancer survivor's quality of life. To date, little is known about local dose-effects after modern radiotherapy including hypofractionation. In the current study we related the local spatial distribution of radiation dose in the rectum to late patient-reported gastrointestinal (GI) toxicities for conventionally fractionated (CF) and hypofractionated (HF) modern radiotherapy in the randomized HYPRO trial. Patients treated to 78 Gy in 2 Gy fractions ( = 298) or 64.6 Gy in 3.4 Gy fractions ( = 295) with available late toxicity questionnaires ( ≥ 2 within 1-5 years post-treatment) and available 3D planning data were eligible for this study. The majority received intensity modulated radiotherapy (IMRT). We calculated two types of dose surface maps: (1) the total delineated rectum with its central axis scaled to unity, and (2) the delineated rectum with a length of 7 cm along its central axis aligned on the prostate's half-height point (prostate-half). For each patient-reported GI symptom, dose difference maps were constructed by subtracting average co-registered EQD2 (equivalent dose in 2 Gy) dose maps of patients with and without the symptom of interest, separately for HF and CF. -values were derived from permutation tests. We evaluated patient-reported moderate to severe GI symptoms. Observed incidences of rectal bleeding and increased stool frequency were significantly higher in the HF group. For rectal bleeding ( = 0.016), mucus discharge ( = 0.015), and fecal incontinence ( = 0.001), significant local dose-effects were observed in HF patients but not in CF patients. For rectal pain, similar local dose-effects ( < 0.05) were observed in both groups. No significant local dose-effects were observed for increased stool frequency. Total rectum mapping vs. prostate-half mapping showed similar results. We demonstrated significant local dose-effect relationships for patient-reported late GI toxicity in patients treated with modern RT. HF patients were at higher risk for increased stool frequency and rectal bleeding, and showed the most pronounced local dose-effects in intermediate-high dose regions. These findings suggest that improvement of current treatment optimization protocols could lead to clinical benefit, in particular for HF treatment.
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http://dx.doi.org/10.3389/fonc.2020.00469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169424PMC
April 2020

Can the Adoption of Hypofractionation Guidelines Expand Global Radiotherapy Access? An Analysis for Breast and Prostate Radiotherapy.

JCO Glob Oncol 2020 04;6:667-678

Dana Farber Cancer Institute, Boston, MA.

Purpose: The limited radiotherapy resources for global cancer control have resulted in increased interest in developing time- and cost-saving innovations to expand access to those resources. Hypofractionated regimens could minimize cost and increase access for limited-resource countries. In this investigation, we estimated the percentage cost-savings per radiotherapy course and increased radiotherapy access in African countries after adopting hypofractionation for breast and prostate radiotherapy. For perspective, results were compared with high-income countries.

Methods: The cost and course of breast and prostate radiotherapy for conventional and hypofractionated regimens in low-resource facilities were calculated using the Radiotherapy Cost Estimator tool developed by the International Atomic Energy Agency (IAEA) and then compared with another activity-based costing model. The potential maximum cost savings in each country over 7 years for breast and prostate radiotherapy were then estimated using cancer incidence data from the Global Cancer Observatory database with use rates applied. The increase in radiotherapy access was estimated by current national capacities from the IAEA directory.

Results: The estimated cost per course of conventional and hypofractionated regimens were US$2,232 and $1,339 for breast treatment, and $3,389 and $1,699 for prostate treatment, respectively. The projected potential maximum cost savings with full hypofractionation implementation were $1.1 billion and $606 million for breast and prostate treatment, respectively. The projected increase of radiotherapy access due to implementing hypofractionation varied between +0.3% to 25% and +0.4% to 36.0% for breast and prostate treatments, respectively.

Conclusion: This investigation demonstrates that adopting hypofractionated regimens as standard treatment of breast and prostate cancers can result in substantial savings and increase radiotherapy access in developing countries. Given reduced delivery cost and treatment times, we anticipate a substantial increase in radiotherapy access with additional innovations that will allow progressive hypofractionation without compromising quality.
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http://dx.doi.org/10.1200/JGO.19.00261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193821PMC
April 2020

Challenges in Reporting the Effect of Radiotherapy on Erectile Function.

J Sex Med 2020 06 17;17(6):1053-1059. Epub 2020 Apr 17.

Department of Neuroscience, Duke University, Durham, NC, USA; Department of Radiation Oncology, Duke Cancer Institute, Durham, NC, USA. Electronic address:

Background: Erectile dysfunction (ED) is the most common side effect of prostate radiotherapy (RT), but reported rates over time and across modalities have varied widely.

Aim: To evaluate the published literature between 2002 and 2018 for high quality data utilizing prospectively gathered patient-reported ED, and to summarize the challenges in reporting of RT-induced ED (RIED).

Methods: A PubMed search and literature review was performed to identify articles describing rates of ED before and after definitive external beam RT or brachytherapy without androgen deprivation.

Outcomes: Patient-reported ED, patient and treatment variables, and study follow-up constituted the main outcomes of this study.

Results: 24 articles were identified, reporting RIED rates between 17% and 90%. Variables contributing to this range included patient, treatment, and study characteristics known to impact ED reporting.

Clinical Implications: For future studies, we recommend the use of validated patient-reported questionnaires and reporting of baseline function and comorbidities, RT type and dose, and use of androgen deprivation therapy and erectile aids at the time of ED measurement. With sufficient follow-up to understand the late nature of RIED, these recommendations will improve comparison of results between studies and the applicability of results to patients undergoing pretreatment counseling regarding the risks of RIED.

Strengths & Limitations: The literature search and formulation of results were based on a broad understanding of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and the literature, but because of the focus on data reporting, a comprehensive systematic review of all RIED literature was not performed.

Conclusion: Reported rates of ED after RT vary widely due to differences in patients' baseline reported erectile function, age, comorbidities, and characteristics of the treatment delivered. The methodology of ED measurement has significant impact on the applicability and comparability of results to other studies and clinical practice. Nukala V, Incrocci L, Hunt AA, et al. Challenges in Reporting the Effect of Radiotherapy on Erectile Function. J Sex Med 2020;17:1053-1059.
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http://dx.doi.org/10.1016/j.jsxm.2020.03.008DOI Listing
June 2020

Challenges in Reporting the Effect of Radiotherapy on Erectile Function.

J Sex Med 2020 06 17;17(6):1053-1059. Epub 2020 Apr 17.

Department of Neuroscience, Duke University, Durham, NC, USA; Department of Radiation Oncology, Duke Cancer Institute, Durham, NC, USA. Electronic address:

Background: Erectile dysfunction (ED) is the most common side effect of prostate radiotherapy (RT), but reported rates over time and across modalities have varied widely.

Aim: To evaluate the published literature between 2002 and 2018 for high quality data utilizing prospectively gathered patient-reported ED, and to summarize the challenges in reporting of RT-induced ED (RIED).

Methods: A PubMed search and literature review was performed to identify articles describing rates of ED before and after definitive external beam RT or brachytherapy without androgen deprivation.

Outcomes: Patient-reported ED, patient and treatment variables, and study follow-up constituted the main outcomes of this study.

Results: 24 articles were identified, reporting RIED rates between 17% and 90%. Variables contributing to this range included patient, treatment, and study characteristics known to impact ED reporting.

Clinical Implications: For future studies, we recommend the use of validated patient-reported questionnaires and reporting of baseline function and comorbidities, RT type and dose, and use of androgen deprivation therapy and erectile aids at the time of ED measurement. With sufficient follow-up to understand the late nature of RIED, these recommendations will improve comparison of results between studies and the applicability of results to patients undergoing pretreatment counseling regarding the risks of RIED.

Strengths & Limitations: The literature search and formulation of results were based on a broad understanding of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and the literature, but because of the focus on data reporting, a comprehensive systematic review of all RIED literature was not performed.

Conclusion: Reported rates of ED after RT vary widely due to differences in patients' baseline reported erectile function, age, comorbidities, and characteristics of the treatment delivered. The methodology of ED measurement has significant impact on the applicability and comparability of results to other studies and clinical practice. Nukala V, Incrocci L, Hunt AA, et al. Challenges in Reporting the Effect of Radiotherapy on Erectile Function. J Sex Med 2020;17:1053-1059.
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http://dx.doi.org/10.1016/j.jsxm.2020.03.008DOI Listing
June 2020

Effect of cut on secondary metabolite profile in hydroponically-grown L. seedlings: a metabolomic approach.

Nat Prod Res 2021 Nov 30;35(21):4089-4093. Epub 2020 Jan 30.

Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.

Seedlings of L. (sorrel) were grown in floating system and two consecutive cuts took place: 15 (C1) and 30 (C2) days after sowing. An untargeted metabolomics approach was utilised to fingerprint phenolics and other health-related compounds in sorrel leaves, as well as to unveil differences between the two cuts. The untargeted approach allowed to putatively identify 458 metabolites considering both the cuts. Three new terpenoids and two new phenylpropanoid glycosides (dihydrosyringin and dihydroconiferin) with antifungal and anti-inflammatory activity were annotated. Overall, leaves from C2 had lower level of secondary metabolites (44 were down-accumulated), especially sesquiterpenes and stilbenes. Conversely, anthocyanins showed a relevant increase in C2 than in C1 leaves. The dataset suggests that sorrel leaves represent a good source of nutraceutical compounds and unveils the pivotal effect of pre-harvest factor in secondary metabolite profile.
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http://dx.doi.org/10.1080/14786419.2020.1719490DOI Listing
November 2021

Ethiopia: How the Care of 100 Million People Pivots on a Single Cobalt Teletherapy Machine.

Int J Radiat Oncol Biol Phys 2020 02;106(2):230-235

Department of Radiation Oncology, Erasmus MC, Rotterdam, Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.ijrobp.2019.06.015DOI Listing
February 2020

Iodine Accumulation and Tolerance in Sweet Basil ( L.) With Green or Purple Leaves Grown in Floating System Technique.

Front Plant Sci 2019 18;10:1494. Epub 2019 Dec 18.

Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.

Iodine deficiency is a serious world-wide public health problem, as it is responsible for mental retardation and other diseases. The use of iodine-biofortified vegetables represents a strategic alternative to iodine enriched salt for people with a low sodium diet. However, at high concentrations iodine can be toxic to plants. Therefore, research on plant iodine toxicity is fundamental for the development of appropriate biofortification protocols. In this work, we compared two cultivars of sweet basil ( L.) with different iodine tolerance: "Tigullio," less tolerant, with green leaves, and "Red Rubin," more tolerant and with purple leaves. Four greenhouse hydroponic experiments were conducted in spring and in summer with different concentrations of iodine in the nutrient solution (0.1, 10, 50, 100, and 200 μM), supplied as potassium iodide (KI) or potassium iodate (KIO). Plant growth was not affected either by 10 μM KI or by 100 μM KIO, while KI concentrations higher than 50 μM significantly reduced leaf area, total plant dry matter and plant height. The severity of symptoms increased with time depending on the cultivar and the form of iodine applied. Growth inhibition by toxic iodine concentrations was more severe in "Tigullio" than in "Red Rubin," and KI was much more phytotoxic than KIO. Leaf iodine concentration increased with the iodine concentration in the nutrient solution in both varieties, while the total antioxidant power was generally higher in the purple variety. In both basil cultivars, a strong negative correlation was found between the photosynthesis and the leaf iodine content, with significant differences between the regression lines for "Tigullio" and "Red Rubin." In conclusion, the greater tolerance to iodine of the "Red Rubin" variety was associated with the ability to withstand higher concentrations of iodine in leaf tissues, rather than to a reduced accumulation of this element in the leaves. The high phenolic content of "Red Rubin" could contribute to the iodine tolerance of this purple cultivar.
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http://dx.doi.org/10.3389/fpls.2019.01494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930681PMC
December 2019

Comparison of Tumor Volume Parameters on Prostate Cancer Biopsies.

Arch Pathol Lab Med 2020 Jan 6. Epub 2020 Jan 6.

From the Departments of Pathology (Ms Verhoef, Drs Kweldam, Kümmerlin, and van Leenders), Public Health (Mr Nieboer), Urology (Mr Nieboer, Drs Bangma and Roobol), and Radiotherapy (Dr Incrocci), Erasmus MC University Medical Center, Rotterdam, the Netherlands; and Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada (Dr van der Kwast).

Context.—: Prostate biopsy reports require an indication of prostate cancer volume. No consensus exists on the methodology of tumor volume reporting.

Objective.—: To compare the prognostic value of different biopsy prostate cancer volume parameters.

Design.—: Prostate biopsies of the European Randomized Study of Screening for Prostate Cancer were reviewed (n = 1031). Tumor volume was quantified in 6 ways: average estimated tumor percentage, measured total tumor length, average calculated tumor percentage, greatest tumor length, greatest tumor percentage, and average tumor percentage of all biopsies. Their prognostic value was determined by using either logistic regression for extraprostatic expansion (EPE) and surgical margin status after radical prostatectomy (RP), or Cox regression for biochemical recurrence-free survival (BCRFS) and disease-specific survival (DSS) after RP (n = 406) and radiation therapy (RT) (n = 508).

Results.—: All tumor volume parameters were significantly mutually correlated ( > 0.500, < .001). None were predictive for EPE, surgical margin, or BCRFS after RP in multivariable analysis, including age, prostate-specific antigen, number of positive biopsies, and grade group. In contrast, all tumor volume parameters were significant predictors for BCRFS (all < .05) and DSS (all < .05) after RT, except greatest tumor length. In multivariable analysis including only all tumor volume parameters as covariates, calculated tumor length was the only predictor for EPE after RP ( = .02) and DSS after RT ( = .02).

Conclusions.—: All tumor volume parameters had comparable prognostic value and could be used in clinical practice. If tumor volume quantification is a threshold for treatment decision, calculated tumor length seems preferential, slightly outperforming the other parameters.
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http://dx.doi.org/10.5858/arpa.2019-0361-OADOI Listing
January 2020

Patterns of Care of Cancers and Radiotherapy in Ethiopia.

J Glob Oncol 2019 11;5:1-8

Department of Radiation Oncology, Erasmus MC, Rotterdam, the Netherlands.

Purpose: Radiotherapy (RT) is an essential component of cancer treatment. There is a lack of RT services in sub-Saharan Africa as well as limited knowledge regarding clinical practices. The purpose of this study was to identify and describe the patterns for RT treatment in Ethiopia.

Methods And Materials: We performed a retrospective analysis of 1,823 patients treated with cobalt RT at a large referral hospital in Addis Ababa, Ethiopia, from May 2015 through January 2018. Paper charts were reviewed for patient and treatment characteristics. Descriptive statistics were computed using SPSS (IBM, Armonk, NY).

Results: Among patients treated for cancer, 98% (n = 1,784) were adults, 78% (n = 1,426) were female, 5% (n = 85) were HIV positive, 30% (n = 555) were from Addis Ababa, and the median age was 48 years (interquartile range [IQR], 38-58 years). Cervical cancer was the most frequent cancer treated (47%, n = 851), followed by breast cancer (15%, n = 274) and head and neck cancer (10%, n = 184). Seventy-three percent of patients (n = 1,339) presented at a late stage, and 62% (n = 1,138) received palliative RT. The wait times were the shortest for patients receiving palliative treatment (median, 0 days; IQR, 0-15 days; n = 1,138), whereas wait times were longer for patients receiving curative treatment (median, 150 days; IQR, 60-210 days; n = 685). Three percent of patients (n = 56) had documented grade 3 or 4 acute toxicity; of these, 59% (n = 33) were patients with head and neck cancer.

Conclusion: Cervical cancer accounted for half of patients treated; thus, a majority of patients were adult females. Most patients had advanced-stage cancer, and goals of care were palliative. Wait times were long for patients with curative-intent cancer as a result of low capacity for RT services.
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http://dx.doi.org/10.1200/JGO.19.00129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939739PMC
November 2019

Hydroponically Grown Scop.: Effects of Cut and Storage on Fresh-Cut Produce.

Antioxidants (Basel) 2019 Dec 9;8(12). Epub 2019 Dec 9.

Department of Agriculture, Food and Environment, University of Pisa, 56124 Pisa, Italy.

Wild edible plants have been used in cooking since ancient times. Recently, their value has improved as a result of the scientific evidence for their nutraceutical properties. Scop. (salad burnet) plants were hydroponically grown and two consecutive cuts took place at 15 (C1) and 30 (C2) days after sowing. An untargeted metabolomics approach was utilized to fingerprint phenolics and other health-related compounds in this species; this approach revealed the different effects of the two cuts on the plant. showed a different and complex secondary metabolite profile, which was influenced by the cut. In fact, flavonoids increased in leaves obtained from C2, especially flavones. However, other secondary metabolites were downregulated in leaves from C2 compared to those detected in leaves from C1, as evidenced by the combination of the variable important in projections (VIP score > 1.3) and the fold-change (FC > 2). The storage of leaves for 15 days as fresh-cut products did not induce significant changes in the phenolic content and antioxidant capacity, which indicates that the nutraceutical value was maintained. The only difference evidenced during storage was that leaves obtained from C2 showed a lower constitutive content of nutraceutical compounds than leaves obtained from C1; except for chlorophylls and carotenoids. In conclusion, the cut was the main influence on the modulation of secondary metabolites in leaves, and the effects were independent of storage.
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http://dx.doi.org/10.3390/antiox8120631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943539PMC
December 2019

Apalutamide Sensitizes Prostate Cancer to Ionizing Radiation via Inhibition of Non-Homologous End-Joining DNA Repair.

Cancers (Basel) 2019 Oct 18;11(10). Epub 2019 Oct 18.

Department of Molecular Genetics, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands.

Androgen-deprivation therapy was shown to improve treatment outcome of external beam radiation therapy (EBRT) for locally advanced prostate cancer (PCa). DNA damage response (DDR) was suggested to play a role in the underlying mechanism, but conflicting results were reported. This study aims to reveal the role of the androgen receptor (AR) in EBRT-induced DDR and to investigate whether next-generation AR inhibitor apalutamide can radiosensitize PCa. PCa cell lines and tissue slices were treated with anti-androgen alone or combined with EBRT. The effect of treatments on cell growth, tissue viability, DDR, and cell cycle were investigated. RAD51 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) levels were determined by Western blotting. Homologous recombination (HR) capacity was measured with the directed repeats-green fluorescent protein (DR-GFP) assay. We report the radiosensitizing effect of anti-androgens, which showed synergism in combination with EBRT in AR-expressing tumor slices and cell lines. Moreover, a compromised DDR was observed in AR-expressing cells upon AR suppression. We found that AR inhibition downregulated DNA-PKcs expression, resulting in reduced non-homologous end-joining repair. DDR through HR was a secondary effect due to cell-cycle change. These data provide a mechanistic explanation for the combination regimen and support the clinical use of apalutamide together with EBRT for localized PCa patients.
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http://dx.doi.org/10.3390/cancers11101593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827010PMC
October 2019
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