A Genomic Urine Assay for Surveillance of Patients with Bladder Cancer Treated with Radiotherapy.

Background: Patients with muscle-invasive bladder cancer (MIBC) who receive radiotherapy with curative intent are followed by imaging, cystoscopy, and urine cytology. However, interpretation of cytology and cystoscopy is hampered by the impact of ionizing radiation on cells. Objective: To assess the diagnostic performance of a genomic urine assay to detect urinary tract recurrences in patients with MIBC treated by (chemo)radiation. Design setting and participants: Patients with nonmetastatic MIBC who underwent (chemo)radiation with curative intent from 2016 to 2020 were prospectively included. Follow-up consisted of cystoscopy and upper tract imaging. Prior to cystoscopy, a urine sample was analyzed to assess mutations in the genes FGFR3, HRAS, and TERT and methylation of OTX1, TWIST1, and ONECUT2. The treating physician was blinded for the assay result. Outcome measurements and statistical analysis: The primary endpoint was a urinary tract recurrence. Cross-sectional sensitivity, specificity, and negative predictive value (NPV) were analyzed using a previously developed logistic regression model for the detection of bladder cancer with this assay. The secondary endpoint was the risk of a future urinary tract recurrence following a positive test and negative cystoscopy/imaging, using a time-dependent Cox proportional hazard analysis. Results and limitations: A total of 143 patients were included, and 503 urine samples were analyzed. The median study duration was 20 mo (interquartile range [IQR] 10-33), and the median time to a recurrence was 16 mo (IQR 12-26). In 27 patients, 32 urinary tract recurrences were diagnosed, including three upper tract tumors. Of 32 recurrences, 18 (56%) had a concomitant urine test available. The diagnostic model had an area under the curve of 0.80 (95% confidence interval [CI] 0.69-0.90) with corresponding sensitivity, specificity, and NPV of 78 (95% CI 52-94), 77% (95% CI 73-81), and 99% (95% CI 97-100). When taking into account the anticipatory effect of the test, 28/32 (88%) recurrences were detected. A Cox regression analysis showed a hazard ratio of 14.8 for the development of a future recurrence (p < 0.001). A major limitation was the lack of a concomitant urine test result in 14/32 (44%) recurrences. Conclusions: A genomic urine assay detected urinary tract recurrences after (chemo)radiation in patients with MIBC, and a positive test was strongly associated with future recurrences. Although validation in a large cohort is warranted, the test has the potential to limit frequent cystoscopies. Patient summary: Radiotherapy is a bladder-sparing treatment in patients with bladder cancer. After treatment, these patients undergo visual inspection of the bladder by cystoscopy to detect possible recurrences. However, interpretation of cystoscopy is difficult due to the effects of radiation on the bladder lining. Hence, we analyzed the diagnostic value of a molecular urine test to detect recurrent disease in bladder cancer patients treated by radiotherapy, and we showed that the urine test has the potential to limit the number of cystoscopies.

Mapping of Radiation Oncology and Gynecologic Oncology Services Available to Treat the Growing Burden of Cervical Cancer in Africa.

PURPOSE: To meet the demand for cervical cancer care in Africa, access to surgical and radiation therapy services needs to be understood. We thus mapped the availability of gynecologic and radiation therapy equipment and staffing for treating cervical cancer. METHODS AND MATERIALS: We collected data on gynecologic and radiation oncology staffing, equipment, and infrastructure capacities across Africa. Data was obtained from February to July 2021 through collaboration with international partners using Research Electronic Data Capture. Cancer incidence was taken from the International Agency for Research on Cancer's GLOBOCAN 2020 database. Treatment capacity, including the numbers of radiation oncologists, radiation therapists, physicists, gynecologic oncologists, and hospitals performing gynecologic surgeries, was calculated per 1000 cervical cancer cases. Adequate capacity was defined as 2 radiation oncologists and 2 gynecologic oncologists per 1000 cervical cancer cases. RESULTS: Forty-three of 54 African countries (79.6%) responded, and data were not reported for 11 countries (20.4%). Respondents from 31 countries (57.4%) reported access to specialist gynecologic oncology services, but staffing was adequate in only 11 countries (20.4%). Six countries (11%) reported that generalist obstetrician-gynecologists perform radical hysterectomies. Radiation oncologist access was available in 39 countries (72.2%), but staffing was adequate in only 16 countries (29.6%). Six countries (11%) had adequate staffing for both gynecologic and radiation oncology; 7 countries (13%) had no radiation or gynecologic oncologists. Access to external beam radiation therapy was available in 31 countries (57.4%), and access to brachytherapy was available in 25 countries (46.3%). The number of countries with training programs in gynecologic oncology, radiation oncology, medical physics, and radiation therapy were 14 (26%), 16 (30%), 11 (20%), and 17 (31%), respectively. CONCLUSIONS: We identified areas needing comprehensive cervical cancer care infrastructure, human resources, and training programs. There are major gaps in access to radiation oncologists and trained gynecologic oncologists in Africa.

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate.

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Advances in radiotherapy and its impact on second primary cancer risk: A multi-center cohort study in prostate cancer patients.

BACKGROUND: Modelling studies suggest that advanced intensity-modulated radiotherapy may increase second primary cancer (SPC) risks, due to increased radiation exposure of tissues located outside the treatment fields. In the current study we investigated the association between SPC risks and characteristics of applied external beam radiotherapy (EBRT) protocols for localized prostate cancer (PCa). METHODS: We collected EBRT protocol characteristics (2000-2016) from five Dutch RT institutes for the 3D-CRT and advanced EBRT era (N = 7908). From the Netherlands Cancer Registry we obtained patient/tumour characteristics, SPC data, and survival information. Standardized incidence ratios (SIR) were calculated for pelvis and non-pelvis SPC. Nationwide SIRs were calculated as a reference, using calendar period as a proxy to label 3D-CRT/advanced EBRT. RESULTS: From 2000-2006, 3D-CRT with 68-78 Gy in 2 Gy fractions, delivered with 10-23 MV and weekly portal imaging was the most dominant protocol. By the year 2010 all institutes routinely used advanced EBRT (IMRT, VMAT, tomotherapy), mainly delivering 78 Gy in 2 Gy fractions, using various kV/MV imaging protocols. Sixteen percent (N = 1268) developed ≥ 1 SPC. SIRs for pelvis and non-pelvis SPC (all institutes, advanced EBRT vs 3D-CRT) were 1.17 (1.00-1.36) vs 1.39 (1.21-1.59), and 1.01 (0.89-1.07) vs 1.03 (0.94-1.13), respectively. Nationwide non-pelvis SIR was 1.07 (1.01-1.13) vs 1.02 (0.98-1.07). Other RT protocol characteristics did not correlate with SPC endpoints. CONCLUSION: None of the studied RT characteristics of advanced EBRT was associated with increased out-of-field SPC risks. With constantly evolving EBRT protocols, evaluation of associated SPC risks remains important.

Challenges and opportunities for implementing hypofractionated radiotherapy in Africa: lessons from the HypoAfrica clinical trial.

The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy. Trial registration: Not available yet.

Arbuscular Mycorrhizal Fungi Increase Nutritional Quality of Soilless Grown Lettuce while Overcoming Low Phosphorus Supply.

Lettuce is widely used for its healthy properties, and it is of interest to increase them with minimal environmental impact. The purpose of this work was to evaluate the effect of the arbuscular mycorrhizal fungus (AMF) Funneliformis mosseae in lettuce plants (Lactuca sativa L. cv. Salinas) cultivated in a soilless system with sub-optimal phosphorus (P) compared with non-inoculated controls at two different P concentrations. Results show that lettuce inoculation with the selected AMF can improve the growth and the nutritional quality of lettuce even at sub-optimal P. Leaf content of chlorophylls, carotenoids, and phenols, known as important bioactive compounds for human health, was higher in mycorrhizal lettuce plants compared with non-mycorrhizal plants. The antioxidant capacity in AMF plants showed higher values compared with control plants grown at optimal P nutrition level. Moreover, leaf gas exchanges were higher in inoculated plants than in non-inoculated ones. Nitrogen, P, and magnesium leaf content was significantly higher in mycorrhizal plants compared with non-mycorrhizal plants grown with the same P level. These findings suggest that F. mosseae can stimulate plants growth, improving the nutritional quality of lettuce leaves even when grown with sub-optimal P concentration.

Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel.

BACKGROUND: Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. AIM: We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients' and partners' sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. METHODS: The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995-2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment, according to the nomenclature of the American Urological Association (AUA). Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). OUTCOMES: Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. RESULTS: The guidelines account for patients' cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. CLINICAL IMPLICATIONS: The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. STRENGTHS & LIMITATIONS: The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. CONCLUSION: The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research. Wittmann D, Mehta A, McCaughan E, et al. Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel. J Sex Med 2022;19:1655-1669.

Clinicopathology and Treatment Patterns of Head and Neck Cancers in Ethiopia.

PURPOSE: Head and neck cancers are the third most common cancers treated with radiation in Ethiopia. There is, however, a lack of published data on clinical and pathological characteristics and treatment patterns of head and neck cancers in the country. The objective of the study was to assess clinical and pathological characteristics and treatment patterns of head and neck cancers at Tikur Anbessa Specialized Hospital, which housed the only radiotherapy facility in Ethiopia during the study period. MATERIALS AND METHODS: A retrospective cross-sectional study design with a simple random sampling of histologically confirmed head and neck cancers treated from 2014 to 2017 with analysis of descriptive data. RESULTS: Three hundred twenty-one patient charts were analyzed in this study from a total population of 1,377 from the department cancer registry. The male to female ratio was 2:1. The median age was 45 years (interquartile range, 26-59). The most common primary site of head and neck cancers was nasopharynx (128 of 321, 40%), and the major histologic type was squamous cell carcinoma (285 of 321, 89%). Majority of the cases had advanced disease (stage III-IVC, 221 of 251, 88%), but 92% had potentially curable disease (231 of 321). Cobalt radiotherapy was used for 67% of all patients receiving treatment (184 of 273). Induction chemotherapy followed by radiotherapy was frequently used for curative intent patients (75 of 231, 32%). There was long duration between diagnosis and initiation of treatment, with 56% (148 of 264) waiting longer than 3 months. CONCLUSION: Majority of patients with head and neck cancers seen in Ethiopia presented at advanced stage of disease, received cobalt radiotherapy, and had protracted treatment initiation. These findings underscore the need for additional investments to improve research capacity and increase the availability of high-quality radiotherapy and supportive services to deliver optimal care for patients with head and neck cancer and other cancer patients in the country.

Effect of Blanching and Boiling on the Secondary Metabolism of Cultivated Cardoon Stalks: A Case Study of the Tuscany Region (Italy).

Cardoon (C. cardunculus var. altilis DC) is commonly cultivated in the Mediterranean area to produce stalks that are consumed once cooked. Before cooking, stalks are usually subjected to blanching, which means they are exposed to darkness for a few weeks. The present work analyzed the effect of field blanching carried out for 40 days in different ways (burying the stalks under soil or covering them with plastic sheet) on the total phenolic content (TPC), phenolic profile, cynaropicrin content (a bitter compound), and antioxidant activity (AA) of two cardoon cultivars. The nutraceutical quality of blanched cardoons was also investigated following boiling. The phenolic profile revealed a higher number of compounds in blanched stalks than in raw ones. The cynaropicrin content decreased in both cultivars after blanching, indicating a sensitivity to dark conditions and the effectiveness of blanching method in reducing its bitterness. The data presented contribute to improving the knowledge about the effect of blanching and boiling on the quality of cardoon stalks.

Local Failure Events in Prostate Cancer Treated with Radiotherapy: A Pooled Analysis of 18 Randomized Trials from the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium (LEVIATHAN).

CONTEXT: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. OBJECTIVE: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. EVIDENCE ACQUISITION: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. EVIDENCE SYNTHESIS: The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06-1.30), PCSS (HR 2.02, 95% CI 1.75-2.33), and DMFS (HR 1.94, 95% CI 1.75-2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36-1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21-0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. CONCLUSIONS: Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a "second wave" of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. PATIENT SUMMARY: Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it.

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

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.

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.

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.

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

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 R2 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.

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

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.

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

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 (NTD2Gy)for acute toxicity (α/ß 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 χ2 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 NTD2Gy 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.

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

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.

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

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.

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

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 Pelargonium graveolens 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. P. graveolens 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 P. graveolens may be safely used for the extraction of bioactive molecules.

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

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.

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

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.