[Does radiation therapy for prostate cancer increase the risk of second cancers?] / La radiothérapie du cancer de la prostate augmente-t-elle le risque de seconds cancers ?

PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.

[About a case of primary laryngeal mucosal melanoma in a patient with medical history of oropharyngeal squamous carcinoma]. / À propos d'un cas de mélanome muqueux primitif laryngé chez un patient présentant un antécédent de carcinome épidermoïde de l'oropharynx.

INTRODUCTION: Primary laryngeal mucosal melanoma is a rare tumour with a poor prognosis. Its often difficult diagnosis should rule out laryngeal metastatic localization of cutaneous melanoma. CASE PRESENTATION: We report a case of primary laryngeal mucosal melanoma diagnosed in a 65-year-old man, treated 6 years previously with radio-chemotherapy and surgery for squamous cell carcinoma of the right lateral oropharyngeal region. The definitive diagnosis of primary laryngeal mucosal melanoma was made on the resection specimen, whereas the initial biopsy of the epilaryngeal mass discovered during the patient's surveillance had concluded that it was a laryngeal recurrence of the known squamous cell carcinoma. DISCUSSION: Through this case, we propose to remind the main characteristics and the diagnostic pitfalls of these tumours.

Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review.

Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2-169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4-409.2 months), while the median OS from second cancer was 27.6 months (range: 1-117.8 months). The SIR was 0.86 (95% CI: 0.54-1.30) for males and 1.13 (95% CI: 0.36-2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm.

Risk of Secondary Malignancies After Pelvic Radiation: A Population-based Analysis.

Background and objective: Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies. Methods: A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation. Key findings and limitations: A total of 2 102 192 patients were analyzed (1 189 108 with prostate, 315 026 with bladder, 88 809 with cervical, 249 535 with uterine, and 259 714 with rectal/anal cancer). The incidence rate (defined as cases per 1000 person years) of any secondary malignancies (including but not limited to secondary pelvic malignancies) was higher in radiation patients than in nonradiation patients (incidence rate ratio [IRR] 1.04, confidence interval [CI] 1.03-1.05), with significantly greater rates noted in radiation patients with prostate (IRR 1.22, CI 1.21-1.24), uterine (IRR 1.34), and cervical (IRR 1.80, CI 1.72-1.88) cancer. While the overall incidence rate of any secondary pelvic malignancy was lower in radiation patients (IRR 0.79, CI 0.78-0.81), a greater incidence was still noted in the same cohorts including radiation patients with prostate (IRR 1.42, CI 1.39-1.45), uterine (IRR 1.15, CI 1.08-1.21), and cervical (IRR 1.72, CI 1.59-1.86) cancer. Conclusions and clinical implications: Except for localized cervical cancer, when put in the context of median overall survival, the impact of radiation likely does not carry enough weight to change practice patterns. Radiation for pelvic malignancies increases the risk for several secondary malignancies, and more specifically, secondary pelvic malignancies, but with a relatively low absolute risk of secondary malignancies, the benefits of radiation warrant continued use for most pelvic malignancies. Practice changes should be considered for radiation utilization in malignancies with excellent cancer-specific survival such as cervical cancer. Patient summary: The use of radiation for the management of pelvic malignancies induces a risk of secondary malignancies to its recipients. However, the absolute risk being low, the benefits of radiation warrant its continued use, and a change in practice patterns is unlikely.

Long-term second primary cancer risk in adolescent and young adult (15-39 years) cancer survivors: a population-based study in the Netherlands between 1989 and 2018.

BACKGROUND: Few studies have comprehensively investigated the long-term second cancer risk among adolescent and young adult (AYA, aged 15-39 years) cancer survivors. This study investigated the long-term second cancer risk by including the full range of first and second cancer combinations with at least 10 observations in the Netherlands between 1989 and 2018. MATERIALS AND METHODS: First and second primary cancer data of all 6-month AYA cancer survivors were obtained from the nationwide population-based Netherlands Cancer Registry. Excess cancer risk compared to the general population was assessed with standardized incidence ratio (SIR) and absolute excess risk (AER) statistics up to 25 years after diagnosis. Cumulative incidences were estimated, using death as a competing risk factor. Analyses were carried out with and without applying multiple cancer rules. RESULTS: The cohort included 99 502 AYA cancer survivors. Male survivors had a 2-fold higher risk of developing any cancer compared to the general population, whereas this was around 1.3-fold in females. AERs were 17.5 and 10.1 per 10 000 person-years for males and females. The long-term excess risk of cancer was significantly higher for most first and second primary cancer combinations, but comparable and lower risk estimates were also observed. Application of the multiple cancer rules resulted in a noticeable risk underestimation in melanoma, testicular, and breast cancer survivors. Risk outcomes remained similar in most cases otherwise. The cumulative incidence of second cancer overall increased over time up to 8.9% in males and 10.3% in females at 25 years' follow-up. Highest long-term cumulative incidences were observed among lymphoma survivors (13.3% males and 18.9% females). CONCLUSIONS: AYA cancer survivors have a higher cancer risk compared to the general population for most cancers up to 25 years after their initial cancer diagnosis. Additional studies that investigate risk factors for the specific cancer type combinations are needed to develop personalized follow-up strategies.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Patient-Reported Outcomes of Accelerated Aging: A Novel Approach to Investigate Second Cancer Risk in Adolescent and Young Adult (18-39 Years) Cancer Survivors.

BACKGROUND: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. PATIENTS AND METHODS: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. RESULTS: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. CONCLUSION: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.

Susceptibility Genes Associated with Multiple Primary Cancers.

With advancements in treatment and screening techniques, we have been witnessing an era where more cancer survivors harbor multiple primary cancers (MPCs), affecting approximately one in six patients. Identifying MPCs is crucial for tumor staging and subsequent treatment choices. However, the current clinicopathological criteria for clinical application are limited and insufficient, making it challenging to differentiate them from recurrences or metastases. The emergence of next-generation sequencing (NGS) technology has provided a genetic perspective for defining multiple primary cancers. Researchers have found that, when considering multiple tumor pairs, it is crucial not only to examine well-known essential mutations like MLH1/MSH2, EGFR, PTEN, BRCA1/2, CHEK2, and TP53 mutations but also to explore certain pleiotropic loci. Moreover, specific deleterious mutations may serve as regulatory factors in second cancer development following treatment. This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.

Out-of-Field Dose Measurement by TLD Dosimetry and Estimation of Radiation-Induced Secondary Cancer Risk of Thyroid and Breast from Head Radiotherapy.

Background: Radiation therapy, the most common form of cancer treatment, can result in late complications, such as secondary breast and thyroid cancers. Objective: This study aimed to evaluate the risk of secondary cancers using two radiobiological models of Excess Absolute Risk (EAR) and Excess Relative Risk (ERR) in patients with brain cancer undergoing radiotherapy for improved survival rates of cancer patients. Material and Methods: In this expository cross-sectional study, 45 patients under the age of 40 years underwent Whole Brain Radiotherapy (WBRT) using a compact accelerator in Shahid Ramezanzadeh Hospital, Yazd, Iran. Out-of-field organ dose measurement was performed using a Thermoluminescent Dosimeter (TLD) to determine the dose to thyroid and breast tissues. The risk of secondary cancers in these organs was calculated 3, 5, 10, 15, and 20 years after radiation therapy. Results: The mean values of thyroid cancer risk in men and women were 0.418±0.509 and 0.274±0.306, respectively. ERR values of breast cancer in 3-, 5-, 10-, 15-, and 20-year women undergoing radiation therapy were 1.084±2.938, 0.594±1.407, 0.248±0.497, 0.138±0.248, and 0.091±0.148, respectively. EAR values of breast cancer in 3-, 5-, 10-, 15-, and 20-year women following radiation therapy were 0.064±0.060, 0.077±0.071, 0.119±0.100, 0.178±0.248, and 0.259±0.178, respectively. Conclusion: After irradiation, the risk of secondary cancer is affected by factors, such as the patient's age and gender. The secondary thyroid cancer is higher than that of other organs, such as the breast, in the patients undergoing WBRT.

Long-term outcome of patients with peripheral ground-glass opacity-dominant lung cancer after sublobar resections.

OBJECTIVE: This study aimed to evaluate the long-term prognosis of patients with peripheral small ground-glass opacity-dominant lung cancer after sublobar resection. We have already reported the 5-year safety and efficacy of sublobar resection and report the long-term outcomes after a 10-year follow-up period. METHODS: Between May 2009 and April 2011, 333 patients with radiologically noninvasive peripheral lung cancer were enrolled from 51 institutions (median age, 62 years at registration) and followed up until May 6, 2021. Of these patients, sublobar resections with wedge resection as the first choice were performed in 314 patients (258 wedge resections and 56 segmentectomies), conversion lobectomies were performed in 11 patients, and 8 patients were ineligible. RESULTS: The 10-year relapse-free survival and overall survival for the 314 patients with sublobar resections were 98.6% (95% confidence interval, 96.2-99.5) and 98.5% (95% confidence interval, 96.1-99.4), respectively. There was 1 local recurrence at the resection margin. Among the patients, second cancers were observed in 43 patients (13.4%; 95% confidence interval, 9.8-17.6), of which 18 were second lung cancers (5.8%; 95% confidence interval, 3.5-8.9). CONCLUSIONS: Peripheral ground-glass opacity-dominant lung cancer is cured by sublobar resection, with wedge resection as the first choice, and the indications for other treatment options should be further investigated. The incidence of second cancer is similar to that in the general Japanese population.

Evaluation of Second Primary Cancer Risk Among Chronic Lymphocytic Leukemia Patients: Multicenter Study.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary cancers (SPC). The aim of this study is to determine the frequency of SPC in CLL patients and determine the relationship between these cancers and their treatment status, cytogenetic factors, and other risk factors. METHODS: The study was designed as multicenter and retroprospective. The sample comprised 553 subjects with a CLL diagnosis. Data collection commenced in August 2016, and completed at May 2021. RESULTS: Fifty one of 553 patients followed for CLL, had a history of SPC. SPC development rate was 9.2%. Epithelial tumors were mostly observed. According to the incidence skin, lymphoma, renal, breast, lung, gastrointestinal system, thyroid, malignant melanoma, prostate, Kaposi's sarcoma, neuroendocrine tumor, ovarian, larynx and salivary gland cancers were detected respectively. The 13q deletion was the most common genetic abnormality in those who developed SPC, and the frequency of 13q deletion was found to be increased statistically significant in those with malignancy, compared to those who did not. CONCLUSION: In CLL patients with SPC, the age of diagnosis, 13q and CD38 positivity, and treatment rates with fludarabine and monoclonal antibodies were found to be higher. Also, we determined that SPC frequency increased independently from hemogram values (except hemoglobin values), ß2 microglobulin level on admission, number of treatment lines, and genetic mutations other than 13q, in CLL patients. In addition, the mortality rate was higher in CLL patients with SPC and they were prone to be in advanced stages at the time of diagnosis.

Predicting second breast cancer among women with primary breast cancer using machine learning algorithms, a population-based observational study.

Breast cancer survivors often experience recurrence or a second primary cancer. We developed an automated approach to predict the occurrence of any second breast cancer (SBC) using patient-level data and explored the generalizability of the models with an external validation data source. Breast cancer patients from the cancer registry of Zurich, Zug, Schaffhausen, Schwyz (N = 3213; training dataset) and the cancer registry of Ticino (N = 1073; external validation dataset), diagnosed between 2010 and 2018, were used for model training and validation, respectively. Machine learning (ML) methods, namely a feed-forward neural network (ANN), logistic regression, and extreme gradient boosting (XGB) were employed for classification. The best-performing model was selected based on the receiver operating characteristic (ROC) curve. Key characteristics contributing to a high SBC risk were identified. SBC was diagnosed in 6% of all cases. The most important features for SBC prediction were age at incidence, year of birth, stage, and extent of the pathological primary tumor. The ANN model had the highest area under the ROC curve with 0.78 (95% confidence interval [CI] 0.750.82) in the training data and 0.70 (95% CI 0.61-0.79) in the external validation data. Investigating the generalizability of different ML algorithms, we found that the ANN generalized better than the other models on the external validation data. This research is a first step towards the development of an automated tool that could assist clinicians in the identification of women at high risk of developing an SBC and potentially preventing it.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma

Background and purpose To predict treatment-related cardiovascular disease (CVD) and second cancer 30-yea. absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. Material and methods This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016–2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose–response relationships. Results Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4–6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2–23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. Conclusion For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects (AU)

Treating secondary malignant neoplasms: A burden of childhood cancer survivors.

Each year approximately 35,000 children and adolescents are diagnosed with cancer in Europe. Five-year survival rates have improved and now reach 80% in most European countries, thanks to a combination of chemotherapy, radiotherapy, and surgery. To date, there are more than 44,000 Italians still living several years after being diagnosed with cancer in developmental age. The risk of premature morbidity and mortality for cancer survivors is well known and documented. Approximately 60% of survivors of cancer in childhood and adolescence have at least one chronic health condition in later life, and more than one in four develop severe or life-threatening disorders. Among the various long-term iatrogenic sequelae of cancer treatments, the most worrisome are second malignant neoplasms. We reported on our mono-institutional experiences of screening and treating secondary breast cancer, secondary thyroid cancer and secondary osteosarcoma. Recommendations on the surveillance needed for cancer survivors because of the risk of late effects of their disease or its treatment suggest that discussing the potential problems early on can be crucial to a patient's future health. These considerations and our consolidated experience strengthen our conviction that survivors of cancer in childhood and adolescence who develop second malignant neoplasms should be treated at highly-specialized centers. Multidisciplinary care requires close communications and high levels of up-to-date professional expertise. This challenging area of health care is also changing rapidly because cancer survivorship is a work in progress, but we cannot wait for definitive conclusions on many aspects because this will take decades, especially for pediatric patients.

Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis.

BACKGROUND: Second primary cancer incidence is rising among breast cancer survivors. We examined the risks of non-breast second primaries, in combination and at specific cancer sites, through a systematic review and meta-analysis. METHODS: We conducted a systematic search of PubMed, Embase, and Web of Science, seeking studies published by March 2022. We included studies that reported standardized incidence ratios (SIRs), with associated standard errors, assessing the combined risk of second non-breast primaries following breast cancer. We performed meta-analyses of combined second primary risks, stratifying by age, follow-up duration, and geographic region. We also assessed second primary risks at several specific sites, stratifying by age. The inverse variance method with DerSimonian-Laird estimators was used in all meta-analyses, assuming a random-effects model. Associated biases and study quality were evaluated using the Newcastle-Ottawa scale. RESULTS: One prospective and twenty-seven retrospective cohort studies were identified. SIRs for second non-breast primaries combined ranged from 0.84 to 1.84. The summary SIR estimate was 1.24 (95% CI 1.14-1.36, I2: 99%). This varied by age: the estimate was 1.59 (95% CI 1.36-1.85) when breast cancer was diagnosed before age 50, which was significantly higher than in women first diagnosed at 50 or over (SIR: 1.13, 95% CI 1.01-1.36, p for difference: < 0.001). SPC risks were also significantly higher when based on Asian, rather than European, registries (Asia-SIR: 1.47, 95% CI 1.29-1.67. Europe-SIR: 1.16, 95% CI 1.04-1.28). There were significantly increased risks of second thyroid (SIR: 1.89, 95% CI 1.49-2.38), corpus uteri (SIR: 1.84, 95% CI 1.53-2.23), ovary (SIR: 1.53, 95% CI 1.35-1.73), kidney (SIR: 1.43, 95% CI 1.17-1.73), oesophagus (SIR: 1.39, 95% CI 1.26-1.55), skin (melanoma) (SIR: 1.34, 95% CI 1.18-1.52), blood (leukaemia) (SIR: 1.30, 95% CI 1.17-1.45), lung (SIR: 1.25, 95% CI 1.03-1.51), stomach (SIR: 1.23, 95% CI 1.12-1.36) and bladder (SIR: 1.15, 95% CI 1.05-1.26) primaries. CONCLUSIONS: Breast cancer survivors are at significantly increased risk of second primaries at many sites. Risks are higher for those diagnosed with breast cancer before age 50 and in Asian breast cancer survivors compared to European breast cancer survivors. This study is limited by a lack of data on potentially confounding variables. The conclusions may inform clinical management decisions following breast cancer, although specific clinical recommendations lie outside the scope of this review.

The role of image-guided radiotherapy in prostate cancer: A systematic review and meta-analysis.

Background: Image-guided radiotherapy (IGRT) has gradually been widely promoted in clinical procedure. However, there has been no consensus on the effects of IGRT on toxicity and survival, and no clear level 1 evidence has even been promulgated. Methods: Medline, EMBASE, PubMed, Cochrane databases and ClinicalTrials.gov were searched for studies comparing IGRT vs non-IGRT or higher frequency IGRT vs lower frequency IGRT during prostate radiotherapy, indexed from database inception to April 2022. Results: The review included 18 studies (3 randomized clinical trial and 15 cohort studies) involving 6521 men, with a median duration of patient follow-up of 46.2 months in the IGRT group vs 52.7 months in the control group. The meta-analysis demonstrated that IGRT significantly reduced acute GU (risk ratio [RR], 0.78; 95 % confidence interval [CI], 0.69-0.88; P < 0.001 [9 studies]) and GI toxicity (RR, 0.49; 95 % CI, 0.35-0.68; P < 0.001 [4 studies]) and late GI toxicity (HR, 0.25; 95 % CI, 0.07-0.87; P = 0.03 [3 studies]) compared with non-IGRT. Meanwhile, compared with prospective studies, retrospective studies showed that IGRT had a more significant effect in reducing the late GI toxicity. Compared with non-daily IGRT, daily IGRT significantly improved 3-year PRFS (HR, 0.45; 95 % CI, 0.28-0.72; P = 0.001 [2 studies]) and BFFS (HR, 0.57; 95 % CI, 0.39-0.83; P = 0.003 [3 studies]). Furthermore, high-frequency daily IGRT could lead to greater 3-year BFFS benefit in prostate cancer patients than weekly IGRT. However, no significant effects of IGRT on acute rectal toxicity, late GU toxicity, 5-year OS and SCM were found. Conclusions: For men receiving prostate radiotherapy, IGRT was associated with an improvement in biochemical tumor control and a reduction in GI and acute GU toxicity, but did not significantly improve 5-year OS or increase 5-year SCM.

Prolonged gut microbial alterations in post-transplant survivors of allogeneic haematopoietic stem cell transplantation.

Dysbiosis of the gut microbiota has been reported to increase early complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, it remains unclear whether gut microbial alterations persist during late complications, such as chronic graft-versus-host disease (cGVHD) or secondary cancers. Here, we analysed the gut microbiota of 59 patients who survived for 1-21.7 years (median, 6.4 years) after allo-HSCT. Long-term survivors showed lower gut microbial diversity than the age- and sex-matched healthy controls. This decreased diversity was reflected in the reduced abundance of the butyrate-producing bacteria. Patients with a history of grade 3 acute graft-versus-host disease (aGVHD) exhibited higher Veillonella abundance than patients with a history of grade 1-2 or non-aGVHD cases. The abundance of Faecalibacterium showed no decrease only in limited cGVHD cases. Additionally, the microbial structure in the secondary cancer group was significantly different (p < 0.05) from that in the non-secondary cancer group. This study is the first to show that microbial dysbiosis is present over a 10-year lifetime after discharge following allo-HSCT. Our results suggest that these prolonged gut microbial alterations may be associated with the development and exacerbation of late complications in post-transplant survivors.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. MATERIAL AND METHODS: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose-response relationships. RESULTS: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. CONCLUSION: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects.