Cancer Research in Vulnerable Populations: A Call for Collaboration and Sustainability From MENAT Countries.

PURPOSE: Cancer is a major burden across Middle East, North Africa, Türkiye (MENAT). Many MENAT countries experience multiple conflicts that compound vulnerabilities, but little research investigates the linkages between vulnerability and cancer research. This study examines the current level and the potential for cancer research among vulnerable populations in the MENAT region, aiming to provide direction toward developing a research agenda on the region's vulnerable populations. METHODS: Expert-driven meetings were arranged among the 10 authors. After obtaining institutional review board approval, a self-administered online survey questionnaire was circulated to more than 500 cancer practitioners working in 22 MENAT countries. RESULTS: Two hundred sixteen cancer practitioners across the MENAT region responded. Fifty percent of the respondents identified clinical research in vulnerable patients with cancer as a significant issue; 21.8% reported previous research experience that included vulnerable populations, and 60% reported encountering vulnerable populations in their daily clinical practice. The main barriers to conducting research were lack of funding (60%), protected time (42%), and research training (35%). More than half of the respondents believed that wars/conflicts constituted an important source of vulnerability. The most vulnerable cancer populations were the elderly, palliative/terminally ill, those with concomitant mental health-related issues, those with other chronic illnesses, and socioeconomically deprived patients. CONCLUSION: Results support that a major effort is needed to improve cancer research among vulnerable cancer populations in the MENAT region. We call for interdisciplinary research that accounts for the region's unique, compounding, and cumulative forms of vulnerability. This cancer research agenda on different vulnerable populations must balance sociobehavioral studies that explore sociopolitical barriers to quality care and clinical studies that gauge and refine treatment protocols. Building a research agenda through collaboration and solidarity with international partners is prime time.

Salvage Whole-Pelvic Radiation and Long-Term Androgen-Deprivation Therapy in the Management of High-Risk Prostate Cancer: Long-Term Update of the McGill 0913 Study.

PURPOSE: To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT (LT-ADT). MATERIALS AND METHODS: From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. RESULTS: At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 µg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. CONCLUSIONS: Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.

Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature.

BACKGROUND: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. METHODS: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. FINDINGS: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. INTERPRETATION: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.

Radiation-Induced Sarcomas of the Breast: A Review of a 20-Year Single-Center Experience.

Background Radiation-induced sarcomas (RISs) are histologically proven sarcomas within or around a previously irradiated site, per Cahan's criteria. RIS incidence is higher in breast cancer compared to other solid cancers and the prognosis remains poor given limited treatment options. This study aimed to review 20-year experience with RISs at a large tertiary care center. Methodology Using our institutional cancer registry database, we included patients meeting Cahan's criteria diagnosed between 2000 and 2020. Patient demographics, oncologic treatment, and oncologic outcomes data were collected. Descriptive statistics were used to describe demographic data. Oncologic outcomes were assessed using the Kaplan-Meier method. Results A total of 19 patients were identified. The median age at RIS diagnosis was 72 years (range = 39-82 months), and the median latency period for the development of RIS was 112 months (range = 53-300 months). All patients underwent surgery, three patients received systemic therapy, and six patients received re-irradiation as salvage treatment. The median follow-up time was 31 months (range = 6-172 months) from the diagnosis of RIS. Overall, five patients had local recurrence, and one patient developed distant metastases. The median time to progression was seven months (range = 4-14 months). The progression-free survival (95% confidence interval (CI)) at two years was 56.1% (37.4-84.4%). At follow-up two years after the diagnosis of sarcoma, the overall survival (95% CI) was 88.9% (75.5-100%). Conclusions While breast RIS remains rare, when managed in a large tertiary care center, overall survival outcomes appear favorable. A significant proportion of patients recur locally after maximal treatment and require salvage therapy to improve outcomes. These patients should be managed in high-volume centers where multidisciplinary expertise is available.

Is Postoperative Radiotherapy Needed in the Management of Adult Craniopharyngiomas?

BACKGROUND: The optimal treatment of adult craniopharyngioma (CP) remains controversial. Although benign, these tumors tend to recur locally. The choice between gross total resection (GTR) versus subtotal resection (STR) with adjuvant or delayed radiotherapy (RT) is debated. The objective of this study is to review our experience with adult CPs over a 20-year period and identify an optimal management strategy. METHODS: From 1999 to 2020, we reviewed all patients diagnosed with CP at our institution. We collected data regarding tumor characteristics, treatments, and toxicity. Disease progression was defined as growth on imaging. Descriptive statistics were used to assess patient characteristics. The Kaplan Meier method was used to assess progression-free survival (PFS) and corresponding 95% confidence intervals (CI) from the time since treatment initiation. RESULTS: Twenty-four patients with a median age of 50 were included in this study. The median follow-up was 85 months. Seven patients had initial GTR, 10 STR, and 7 STR + RT. The overall 5-year PFS was 56% (95% CI: 38-83%): 100% in the STR + RT group, 69% in the GTR group, and 18% in the STR group (p = 0.01). Of the 17 patients initially treated with surgery alone, 3 with GTR and 6 with STR required salvage RT at a median of 46 months, with no further progression after salvage RT. CONCLUSIONS: Our study underscores the importance of RT for local control and suggests that STR + RT should be considered a viable option in the management of these tumors as it may be associated with improved PFS compared to surgery alone.

A Scalable Radiomics- and Natural Language Processing-Based Machine Learning Pipeline to Distinguish Between Painful and Painless Thoracic Spinal Bone Metastases: Retrospective Algorithm Development and Validation Study.

BACKGROUND: The identification of objective pain biomarkers can contribute to an improved understanding of pain, as well as its prognosis and better management. Hence, it has the potential to improve the quality of life of patients with cancer. Artificial intelligence can aid in the extraction of objective pain biomarkers for patients with cancer with bone metastases (BMs). OBJECTIVE: This study aimed to develop and evaluate a scalable natural language processing (NLP)- and radiomics-based machine learning pipeline to differentiate between painless and painful BM lesions in simulation computed tomography (CT) images using imaging features (biomarkers) extracted from lesion center point-based regions of interest (ROIs). METHODS: Patients treated at our comprehensive cancer center who received palliative radiotherapy for thoracic spine BM between January 2016 and September 2019 were included in this retrospective study. Physician-reported pain scores were extracted automatically from radiation oncology consultation notes using an NLP pipeline. BM center points were manually pinpointed on CT images by radiation oncologists. Nested ROIs with various diameters were automatically delineated around these expert-identified BM center points, and radiomics features were extracted from each ROI. Synthetic Minority Oversampling Technique resampling, the Least Absolute Shrinkage And Selection Operator feature selection method, and various machine learning classifiers were evaluated using precision, recall, F1-score, and area under the receiver operating characteristic curve. RESULTS: Radiation therapy consultation notes and simulation CT images of 176 patients (mean age 66, SD 14 years; 95 males) with thoracic spine BM were included in this study. After BM center point identification, 107 radiomics features were extracted from each spherical ROI using pyradiomics. Data were divided into 70% and 30% training and hold-out test sets, respectively. In the test set, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of our best performing model (neural network classifier on an ensemble ROI) were 0.82 (132/163), 0.59 (16/27), 0.85 (116/136), and 0.83, respectively. CONCLUSIONS: Our NLP- and radiomics-based machine learning pipeline was successful in differentiating between painful and painless BM lesions. It is intrinsically scalable by using NLP to extract pain scores from clinical notes and by requiring only center points to identify BM lesions in CT images.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience.

Purpose/objectives: High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. Materials/methods: We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. Results: From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. Conclusions: To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

Awareness and practices of Arab oncologists towards oncofertility in young women with cancer.

Background: Cancer in young women is a major health problem in the Middle Eastern and North African population. We explored the awareness, barriers and practice of Arab oncologists towards oncofertility. Methods: Oncologists from Arab countries treating female cancer patients were invited to complete a 30-item web-based questionnaire that explores oncologists' demographics, available techniques and barriers to oncofertility. Results: 170 oncologists working in 9 different Arab countries responded to the questionnaire. Among the responders, 89 (52.4%) were from Egypt and the central region, 60 (35.3%) were from North Africa and 21 (12.4%) were from the Gulf region.While most participants considered a dedicated training 'necessary', only 43 oncologists (25.3%) received a formal training. Only 17 participants (10%) had a fertility clinic in their centre, 44 (25.9%) and 13 (7.6%) had to refer patients to other centres or other cities, respectively. A total of 96 oncologists (56.5%) did not have access to a fertility preservation service.Out of 147 responders, 79 (53.7%) offered fertility preservation only in patients presenting with early disease and 38 (25.9%) did not offer fertility preservation. In terms of proposed strategies, 50 responders (29.4%) offered embryo cryopreservation, 79 (46.5%) oocyte cryopreservation and 48 (28.2%) ovarian tissue cryopreservation. Conclusion: A large gap exists between international clinical practice guidelines and current practices of fertility preservation in Arab countries. Barriers to optimum service delivery include the lack of physician awareness/training, unavailability of some advanced techniques and a lack of dedicated fertility clinics within the cancer centres.

Radiomics-based machine learning models to distinguish between metastatic and healthy bone using lesion-center-based geometric regions of interest.

Radiomics-based machine learning classifiers have shown potential for detecting bone metastases (BM) and for evaluating BM response to radiotherapy (RT). However, current radiomics models require large datasets of images with expert-segmented 3D regions of interest (ROIs). Full ROI segmentation is time consuming and oncologists often outline just RT treatment fields in clinical practice. This presents a challenge for real-world radiomics research. As such, a method that simplifies BM identification but does not compromise the power of radiomics is needed. The objective of this study was to investigate the feasibility of radiomics models for BM detection using lesion-center-based geometric ROIs. The planning-CT images of 170 patients with non-metastatic lung cancer and 189 patients with spinal BM were used. The point locations of 631 BM and 674 healthy bone (HB) regions were identified by experts. ROIs with various geometric shapes were centered and automatically delineated on the identified locations, and 107 radiomics features were extracted. Various feature selection methods and machine learning classifiers were evaluated. Our point-based radiomics pipeline was successful in differentiating BM from HB. Lesion-center-based segmentation approach greatly simplifies the process of preparing images for use in radiomics studies and avoids the bottleneck of full ROI segmentation.

Cancer Burden Among Arab World Males in 2020: The Need for a Better Approach to Improve Outcome.

PURPOSE: Cancer is a leading cause of increased morbidity and mortality worldwide. This work aims to study the Arab world males' cancers (AMCs) and the similarities and disparities with the world males' cancers (WMCs) from different burden points of view. MATERIALS AND METHODS: A descriptive review of the 2020 Global Cancer Observatory revealed AMCs compared with the 2020 WMCs and the 2018 AMCs. Data on the top 27 AMCs were compared among the region's countries and the world groups. RESULTS: In 2020, a total estimate of 217,203 new AMCs, 2.2% of WMCs, with an average age-standardized rate of 133.5/100,000 population, compared with 222/100,000 population of WMCs, was observed. Death estimates were 148,395, 2.7% of WMCs, with an average age-standardized rate of 95/100,000 population, compared with 120.8/100,000 population of WMCs. The five-year prevalence was observed in 442,014, 1.8% of WMCs. The average AMC mortality to incidence ratio (MIR) was 0.68, compared with 0.55 in WMCs and 0.54 in Arab females. Lung cancer was the top in incidence and mortality, whereas penile cancer was the lowest. The range of MIRs among the 27 cancer types was 0.19-0.96. CONCLUSION: The descriptive review of the 2020 males' cancers in the Arab world revealed a relatively high MIR, compared with males' cancers worldwide and the females' cancers in the Arab world. This requires further evaluation to discern the underlying causes and address them systematically. More cancer control actions are warranted.

Cancer Burden Among Arab-World Females in 2020: Working Toward Improving Outcomes.

PURPOSE: Cancer is the leading cause of morbidity and mortality worldwide. This work presents the Arab-world females' cancers (AFCs) statistics in 2020, compared with the 2018 AFCs statistics, the Arab-world male cancers statistics, and the world females' cancers (WFCs) statistics in 2020. This can help set the stage for a better policy for cancer control programs and improve outcomes. MATERIALS AND METHODS: A descriptive review of the 2020 Global Cancer Observatory concerning AFCs was performed. Data on various cancers were compiled and compared among the countries in the region and WFCs. RESULTS: A total estimate of 244,317 new cases and 132,249 deaths is reported in AFCs; representing 2.65% and 2.99% of WFCs, respectively, with an average crude incidence/mortality ratio of 116.2 (/100,000 population)/62.9 (/100,000 population) and an age-standardized incidence/mortality ratio of 137.7(/100,000 population)/77.2(/100,000 population) compared with 238.8(/100,000 population)/114.6(/100,000 population) and 186(/100,000 population)/84.2(/100,000 population) of WFCs, respectively. Five-year prevalent cases were 585,295; 2.28% of WFCs. In comparison to males, females accounted for 47.8% of the whole population, 52.9% in incidence, 46.9% in mortality, and 56.9% in the prevalence of patients with cancer. Mortality-to-incidence ratio (MIR) was 0.54 (range 0.39-0.62 in Arab countries, compared with 0.48 globally), and it ranged from 0.14 to 0.97 in the 30 AFC types. Breast cancer was the most common cancer in incidence and mortality, with an MIR of 0.39. CONCLUSION: The 2020 descriptive analysis of the females' cancers in the Arab world revealed a relatively high MIR compared with females' cancers worldwide; a lower MIR compared with the males; and comparable MIR to 2018 one. We call for more in-depth studies to determine the causes of these differences that might translate into actionable interventions and better outcomes.

Hypofractionated Radiation Therapy For Diffuse Intrinsic Pontine Glioma: A Noninferiority Randomized Study Including 253 Children.

PURPOSE: Pediatric diffuse intrinsic pontine glioma is an orphen disease. This study aimed to confirm the noninferiority of hypofractionated (HF) radiation therapy. Identification of the prognostic factors that determine the overall survival (OS) and progression-free survival (PFS) was the secondary objective. METHODS AND MATERIALS: We randomized 253 patients into 3 arms of radiation therapy regimens: HF1, receiving 39 Gy in 13 fractions; HF2, receiving 45 Gy in 15 fractions; and conventional fractionation (CF), receiving 54 Gy in 30 fractions. The OS and PFS were calculated using Kaplan-Meier methods, and the noninferiority was estimated against the CF arm. RESULTS: The median OS for the HF1, HF2, and CF were 9.6, 8.2, and 8.7 months, respectively. The 1-, 1.5-, and 2-year OS were 34.6%, 17.9%, and 10.7% for HF1; 26.2%, 13.1%, and 4.8% for HF2; and 25.3%, 12.1%, and 8.4% for CF, respectively (P = .3). The hazard ratio was 0.776 and 1.124 for HF1 and HF2, respectively. Considering the noninferiority margin (Δ) of 15% and a power of 90%, the lower inferiority confidence interval for HF1 was -14.34% and for HF2 it was 11.37% (both below Δ), confirming its noninferiority at 18-months OS. Younger patients (2-5 years of age) had better median OS in the whole cohort (11.6 months), HF1 (13.5), and CF (12.1) but not HF2 (6.2) (P = .003). Furthermore, the OS rates at 1, 1.5, and 2 years for children 2 to 5 years of age in the HF2 arm were lower than those in the HF1 and CF arms. However, similar acute and late side effects were reported in the 3 arms. CONCLUSIONS: Two hypofractionated radiation therapy proved to be noninferior to conventional fractionation. Young age (2-5 years) is the only prognostic factor determining both OS and PFS. The young age superiority was lost with a higher hypofractionated radiation therapy dose, necessitating more caution in applying 45 Gy in 15 fractions in younger children (2-5 years of age).

Development of a generalizable natural language processing pipeline to extract physician-reported pain from clinical reports: Generated using publicly-available datasets and tested on institutional clinical reports for cancer patients with bone metastases.

OBJECTIVE: The majority of cancer patients suffer from severe pain at the advanced stage of their illness. In most cases, cancer pain is underestimated by clinical staff and is not properly managed until it reaches a critical stage. Therefore, detecting and addressing cancer pain early can potentially improve the quality of life of cancer patients. The objective of this research project was to develop a generalizable Natural Language Processing (NLP) pipeline to find and classify physician-reported pain in the radiation oncology consultation notes of cancer patients with bone metastases. MATERIALS AND METHODS: The texts of 1249 publicly-available hospital discharge notes in the i2b2 database were used as a training and validation set. The MetaMap and NegEx algorithms were implemented for medical terms extraction. Sets of NLP rules were developed to score pain terms in each note. By averaging pain scores, each note was assigned to one of the three verbally-declared pain (VDP) labels, including no pain, pain, and no mention of pain. Without further training, the generalizability of our pipeline in scoring individual pain terms was tested independently using 30 hospital discharge notes from the MIMIC-III database and 30 consultation notes of cancer patients with bone metastasis from our institution's radiation oncology electronic health record. Finally, 150 notes from our institution were used to assess the pipeline's performance at assigning VDP. RESULTS: Our NLP pipeline successfully detected and quantified pain in the i2b2 summary notes with 93% overall precision and 92% overall recall. Testing on the MIMIC-III database achieved precision and recall of 91% and 86% respectively. The pipeline successfully detected pain with 89% precision and 82% recall on our institutional radiation oncology corpus. Finally, our pipeline assigned a VDP to each note in our institutional corpus with 84% and 82% precision and recall, respectively. CONCLUSION: Our NLP pipeline enables the detection and classification of physician-reported pain in our radiation oncology corpus. This portable and ready-to-use pipeline can be used to automatically extract and classify physician-reported pain from clinical notes where the pain is not otherwise documented through structured data entry.