Immune cell profiling in Gleason 9 prostate cancer patients treated with brachytherapy versus external beam radiotherapy: An exploratory study.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Results of 15 Gy HDR-BT boost plus EBRT in intermediate-risk prostate cancer: Analysis of over 500 patients.

PURPOSE/OBJECTIVE: To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. RESULTS: 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61-72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88-94)% at 5 years. Five-year FFBF was 94 (89-99)% and 89 (85-94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2-6)% at 5 years. Five-year CI of ADT was 1 (0-3)% and 5 (2-8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95-98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92-98)% in FIR and UIR patients, respectively (p = 0.020). CONCLUSION: In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.

Lives and Economic Loss in Brazil due to Lack of Radiotherapy Access in Cervical Cancer: A Cost-Effectiveness Analysis.

AIMS: Among all malignancies, the use of radiotherapy incurs the highest survival benefit within cervical cancers. Radiotherapy, however, remains underutilised for cervical cancers within the Brazilian public health system (BPHS). The objective of this study was to estimate the potential health and monetary benefits for universal access to radiotherapy and chemoradiotherapy (CRT) for untreated cervical cancer patients in the BPHS. MATERIALS AND METHODS: Using 2016 data on Brazilian cervical cancer incidence and availability of radiotherapy/CRT in the BPHS, the number of cancer deaths due to radiotherapy/CRT underutilisation was estimated. The incremental effectiveness was calculated by life-year gain. The indirect costs from mortality-related productivity loss (MRPL) were estimated based on life expectancy, wage and labour force participation rate. MRPL was compared with direct medical costs after being adjusted to 2016 US dollars. This study was conducted from the payer's perspective; both costs and effectiveness were discounted at a rate of 3%. The incremental cost-effectiveness ratio (ICER) was calculated to determine the cost-effectiveness of radiotherapy for cervical cancer in Brazil. One-way sensitivity analyses were carried out to assess the robustness of the model. RESULTS: The total number of life-years lost due to lack of universal access to radiotherapy and CRT per year were 27 199 and 31 627, respectively. The annual cost to match the radiotherapy gap was $10.5 million, with an additional cost of $3 million to close the CRT gap. The mean years of potential life lost per death was 20.5. The cost per life saved was $7942 for radiotherapy alone (ICER $388/life-year) and $8774 for CRT (ICER $429/life-year). MRPL due to shortage of radiotherapy and CRT were $59 million and $69 million, respectively. CONCLUSION: Providing universal access to radiotherapy/CRT for cervical cancer patients in the BPHS is highly cost-effective and should be prioritised as an impactful public health initiative.

Absolute percentage of biopsied tissue positive for Gleason pattern 4 disease (APP4) appears predictive of disease control after high dose rate brachytherapy and external beam radiotherapy in intermediate risk prostate cancer.

BACKGROUND AND PURPOSE: To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome. MATERIALS AND METHODS: 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD). RESULTS: Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9-6.6) years. Median baseline PSA was 7.3 (5.3-9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75-7.50)%. 38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86. Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1-6.1; p = 0.037) and APP4 (HR 2.3, 1.1-4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4-12.4; p = 0.010) and APP4 (HR 3.7, 1.4-10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9-135.3; p < 0.001). CONCLUSION: APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.

Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System.

AIMS: Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. MATERIALS AND METHODS: Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. RESULTS: Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. CONCLUSION: Thousands of cancer patients requiring radiotherapy do not have access to this treatment in the Brazilian public health system. The shortage of radiotherapy has a significant detrimental effect on cancer survival; over 5000 deaths would probably be prevented in the most common cancer types if radiotherapy access was universal.

The Role of Stereotactic Ablative Body Radiotherapy in Gynaecological Cancers: A Systematic Review.

AIMS: To summarise and evaluate the current literature in gynaecological tumours treated with stereotactic ablative body radiotherapy (SABR) through a systematic review using the Preferred Reported Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. MATERIALS AND METHODS: A literature search through Medline, EMBASE and Cochrane databases resulted in 22 pertinent manuscripts. Selected studies evaluated the locoregional role of SABR in gynaecological tumours, regardless of SABR clinical indication. Data on local control, toxicity and SABR dose and technique were extracted by at least two investigators. RESULTS: In total, 330 patients received locoregional SABR for gynaecological tumour and had measurable clinical outcomes. Six different clinical scenarios were identified: (i) boost to external beam radiotherapy (EBRT) for cervical cancer as radical treatment; (ii) boost to EBRT for non-operable endometrial cancer; (iii) treatment for pelvic and/or para-aortic node metastases; (iv) adjuvant treatment after surgery in uterine/cervix cancers; (v) salvage of non-nodal pelvic recurrences and (vi) vulvar or vaginal malignancies. Except for SABR as a boost for non-operable endometrial cancer, local control over 80% was found in a range of median follow-up of 4-132 months. Local control in non-operable endometrial tumours receiving SABR was 53%. In salvage treatments for non-nodal pelvic relapses, SABR was associated with about a 20% grade 3-4 gastrointestinal toxicity. CONCLUSION: There is no clear consensus or evidence on the defined role of SABR in gynaecological tumours. Local control and toxicity associated with SABR seems reasonable for most clinical indications found by this review with a short median follow-up. When used for salvage of non-nodal pelvic recurrences, SABR may be associated with high rates of grade 3-4 late gastrointestinal toxicity.

Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages.

CBA mouse macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. It has been established that some Leishmania species are destroyed by reactive oxygen species (ROS). However, other species of Leishmania exhibit resistance to ROS or even down-modulate ROS production. We hypothesized that L. amazonensis-infected macrophages reduce ROS production soon after parasite-cell interaction. Employing a highly sensitive analysis technique based on chemiluminescence, the production of superoxide (O(·-)(2)) and hydrogen peroxide (H(2)O(2)) by L. major- or L. amazonensis-infected CBA macrophages were measured. L. major induces macrophages to release levels of (O(·-)(2)) 3·5 times higher than in uninfected cells. This (O(·-)(2)) production is partially dependent on NADPH oxidase (NOX) type 2. The level of accumulated H(2)O(2) is 20 times higher in L. major-than in L. amazonensis-infected cells. Furthermore, macrophages stimulated with L. amazonensis release amounts of ROS similar to uninfected cells. These findings support previous studies showing that CBA macrophages are effective in controlling L. major infection by a mechanism dependent on both (O(·-)(2)) production and H(2)O(2) generation. Furthermore, these data reinforce the notion that L. amazonensis survive inside CBA macrophages by reducing ROS production during the phagocytic process.