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PURPOSE: Prostate cancer has emerged as a significant public health challenge in the Middle East, characterized by rising incidence rates and a concerning mortality-to-incidence ratio. Yet, despite these alarming trends, data regarding prostate cancer awareness in the region remain limited. To address this critical knowledge gap, this study investigates prostate cancer awareness within the Middle East. MATERIALS AND METHODS: A cross-sectional survey was performed among 5,913 men age 40 years and older across 14 Middle Eastern countries between January 1, 2022, and July 31, 2023. Excluding those with a history of prostate cancer, a validated questionnaire assessed prostate cancer awareness. Data were analyzed using frequencies and percentages for categorical variables, medians and ranges for continuous variables, and Pearson chi-square analysis for relationships between education levels and awareness of prostate cancer. RESULTS: The survey achieved a 74.9% response rate, with 4,431 male participants. Regarding prostate cancer awareness, 83.8% of participants had heard of the disease. However, only 31.0% correctly identified it as the most common malignancy in men, and 21.8% believed it affects both sex. Awareness of screening was limited, with just 19.1% recognizing the prostate-specific antigen test's role. Additionally, participants had a pessimistic view, with a mean perception that 75% of patients with prostate cancer die from the disease, rather than from other causes. Higher education levels were associated with significantly increased awareness of prostate cancer (P < .001). CONCLUSION: This study reveals that while general awareness of the disease exists, crucial knowledge deficits regarding risk factors, screening, and prognosis are evident. Addressing these knowledge gaps through culturally tailored education may improve early detection rates, treatment outcomes, and ultimately reduce the burden of prostate cancer in the Middle East.
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Conhecimentos, Atitudes e Prática em Saúde , Neoplasias da Próstata , Humanos , Masculino , Estudos Transversais , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/psicologia , Oriente Médio/epidemiologia , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Idoso , Detecção Precoce de Câncer/psicologiaRESUMO
Introduction: For patients with locally advanced pancreatic cancer (LAPC), who are candidates for radiation therapy, dose-escalated radiation therapy (RT) offers unique benefits over traditional radiation techniques. In this review, we present a historical perspective of dose-escalated RT for LAPC. We also outline advances in SBRT delivery, one form of dose escalation and a framework for selecting patients for treatment with SBRT. Results: Techniques for delivering SBRT to patients with LAPC have evolved considerably, now allowing for dose-escalation and superior respiratory motion management. At the same time, advancements in systemic therapy, particularly the use of induction multiagent chemotherapy, have called into question which patients would benefit most from radiation therapy. Multidisciplinary assessment of patients with LAPC is critical to guide management and select patients for local therapy. Results from ongoing trials will establish if there is a role of dose-escalated SBRT after induction chemotherapy for carefully selected patients. Conclusion: Patients with LAPC have more therapeutic options than ever before. Careful selection for SBRT may enhance patient outcomes, pending the maturation of pivotal clinical trials.
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PURPOSE: Although a contemporary randomized clinical trial has led to the use of whole-pelvic radiation therapy (WPRT), long-term data evaluating a potential reduction in mortality are lacking and are addressed in the current study. MATERIALS AND METHODS: From 2005 to 2015, 350 men with localized, unfavorable-risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy (ADT) and RT plus docetaxel versus ADT and RT. Treatment of the pelvic lymph nodes was at the discretion of the treating physician. Multivariable Cox and Fine and Grays regression analyses were performed to assess whether a significant association existed between radiation treatment volume and all-cause mortality (ACM) and PC-specific mortality (PCSM), respectively, adjusting for known PC prognostic factors and comorbidity. An interaction term between age (categorized by dichotomization at 65 years to enable clinical interpretation and applicability of the results and which approximates the median (66 years [IQR, 61-70]) and radiation treatment volume was included in the analysis. RESULTS: After a median follow-up of 10.20 years (IQR, 7.96-11.41), 89 men died (25.43%); of these, 42 died of PC (47.19%). Of the 350 randomly assigned patients, 88 (25.14%) received WPRT. In men younger than 65 years, WPRT was associated with a significantly lower ACM risk (adjusted hazard ratio [AHR], 0.33 [95% CI, 0.11 to 0.97]; P = .04) and lower PCSM risk (AHR, 0.17 [95% CI, 0.02 to 1.35]; P = .09) after adjusting for covariates, whereas this was not the case for men 65 years or older. CONCLUSION: WPRT has the potential to reduce mortality in younger men with unfavorable-risk PC.
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Pelve , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Idoso , Pessoa de Meia-Idade , Pelve/efeitos da radiação , Antagonistas de Androgênios/uso terapêutico , Linfonodos/patologia , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Irradiação Linfática , Fatores de RiscoRESUMO
PURPOSE: Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. METHODS: This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. RESULTS: Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. CONCLUSIONS: HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial.
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PURPOSE: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. METHODS: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher's exact test. RESULTS: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes-KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63-had significantly lower mRNA expression levels in patients with CP4 compared to those without. CONCLUSIONS: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.
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PURPOSE: Clinical efficiency is a key component of value-based health care. Our objective here was to identify workflow inefficiencies by using time-driven activity-based costing (TDABC) and evaluate the implementation of a new clinical workflow in high-volume outpatient radiation oncology clinics. METHODS: Our quality improvement study was conducted with the Departments of GI, Genitourinary (GU), and Thoracic Radiation Oncology at a large academic cancer center and four community network sites. TDABC was used to create process maps and optimize workflow for outpatient consults. Patient encounter metrics were captured with a real-time status function in the electronic medical record. Time metrics were compared using Mann-Whitney U tests. RESULTS: Individual patient encounter data for 1,328 consults before the intervention and 1,234 afterward across all sections were included. The median overall cycle time was reduced by 21% in GI (19 minutes), 18% in GU (16 minutes), and 12% at the community sites (9 minutes). The median financial savings per consult were $52 in US dollars (USD) for the GI, $33 USD for GU, $30 USD for thoracic, and $42 USD for the community sites. Patient satisfaction surveys (from 127 of 228 patients) showed that 99% of patients reported that their providers spent adequate time with them and 91% reported being seen by a care provider in a timely manner. CONCLUSION: TDABC can effectively identify opportunities to improve clinical efficiency. Implementing workflow changes on the basis of our findings led to substantial reductions in overall encounter cycle times across several departments, as well as high patient satisfaction and significant financial savings.
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Pacientes Ambulatoriais , Radioterapia (Especialidade) , Fluxo de Trabalho , Humanos , Radioterapia (Especialidade)/economia , Radioterapia (Especialidade)/métodos , Radioterapia (Especialidade)/normas , Masculino , Feminino , Encaminhamento e Consulta , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Although prostate cancer is a prevalent malignancy worldwide, its clinical presentation and management in the Middle East are not well-documented. This study aims to provide insights into the initial clinical presentation and management of prostate cancer in this region. METHODS: A retrospective review was conducted on seven institutional databases from six Middle Eastern countries, including Türkiye, Lebanon, Iraq, Syria, Bahrain, and Jordan, to identify patients diagnosed with prostate cancer in 2021. Descriptive analysis was performed on the collected data to provide an overview of the demographic, clinical, and treatment variables. RESULTS: A total of 1,136 patients were identified with a median age of 70 (range, 50-84). Most patients (78%) received their prostate cancer diagnosis after presenting with symptoms, as opposed to routine PSA screening. At the time of diagnosis, 35% of men had clinical T3 or T4 disease, 54% with Stage IV disease and 50% with Gleason score ≥ 8. Regarding treatment, 20% of non-metastatic and 22% of metastatic patients received no treatment. CONCLUSION: Most men in this study sought prostate cancer evaluation due to symptoms and were subsequently diagnosed with advanced-stage disease, providing a foundation for future research aimed at understanding the underlying factors behind the observed trends and enabling informed interventions.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Iraque , Líbano/epidemiologia , Estadiamento de NeoplasiasRESUMO
Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information. Here, we investigated the optimal methods for using LLMs to extract six SDoH categories from narrative text in the EHR: employment, housing, transportation, parental status, relationship, and social support. The best-performing models were fine-tuned Flan-T5 XL for any SDoH mentions (macro-F1 0.71), and Flan-T5 XXL for adverse SDoH mentions (macro-F1 0.70). Adding LLM-generated synthetic data to training varied across models and architecture, but improved the performance of smaller Flan-T5 models (delta F1 + 0.12 to +0.23). Our best-fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models in the zero- and few-shot setting, except GPT4 with 10-shot prompting for adverse SDoH. Fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p < 0.05). Our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. These results demonstrate the potential of LLMs in improving real-world evidence on SDoH and assisting in identifying patients who could benefit from resource support.
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BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma. METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six academic sites in the USA. Eligible patients were randomly assigned (1:1), with block randomisation (block sizes of 6-12) with a maximum of 24 patients per group, to receive daily avasopasem (90 mg) or placebo intravenously directly before (ie, within 180 min) SBRT (50, 55, or 60 Gy in five fractions, adaptively assigned in real time by Bayesian estimates of 90-day safety and efficacy). Patients and physicians were masked to treatment group allocation, but not to SBRT dose. The primary objective was to find the optimal dose of SBRT with avasopasem or placebo as determined by the late onset EffTox method. All analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT03340974, and is complete. FINDINGS: Between Jan 25, 2018, and April 29, 2020, 47 patients were screened, of whom 42 were enrolled (median age was 71 years [IQR 63-75], 23 [55%] were male, 19 [45%] were female, 37 [88%] were White, three [7%] were Black, and one [2%] each were unknown or other races) and randomly assigned to avasopasem (n=24) or placebo (n=18); the placebo group was terminated early after failing to meet prespecified efficacy parameters. At data cutoff (June 28, 2021), the avasopasem group satisfied boundaries for both efficacy and toxicity. Late onset EffTox efficacy response was observed in 16 (89%) of 18 patients at 50 Gy and six (100%) of six patients at 55 Gy in the avasopasem group, and was observed in three (50%) of six patients at 50 Gy and nine (75%) of 12 patients at 55 Gy in the placebo group, and the Bayesian model recommended 50 Gy or 55 Gy in five fractions with avasopasem for further study. Serious adverse events of any cause were reported in three (17%) of 18 patients in the placebo group and six (25%) of 24 in the avasopasem group. In the placebo group, grade 3 adverse events within 90 days of SBRT were abdominal pain, acute cholangitis, pyrexia, increased blood lactic acid, and increased lipase (one [6%] each); no grade 4 events occurred. In the avasopasem group, grade 3-4 adverse events within 90 days of SBRT were acute kidney injury, increased blood alkaline phosphatase, haematoma, colitis, gastric obstruction, lung infection, abdominal abscess, post-surgical atrial fibrillation, and pneumonia leading to respiratory failure (one [4%] each).There were no treatment-related deaths but one late death in the avasopasem group due to sepsis in the setting of duodenal obstruction after off-study treatment was reported as potentially related to SBRT. INTERPRETATION: SBRT that uses 50 or 55 Gy in five fractions can be considered for patients with localised pancreatic ductal adenocarcinoma. The addition of avasopasem might further enhance disease outcomes. A larger phase 2 trial (GRECO-2, NCT04698915) is underway to validate these results. FUNDING: Galera Therapeutics.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Radiocirurgia , Humanos , Masculino , Feminino , Idoso , Adenocarcinoma/radioterapia , Adenocarcinoma/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/tratamento farmacológico , Radiocirurgia/efeitos adversos , Teorema de Bayes , Carcinoma Ductal Pancreático/radioterapia , Carcinoma Ductal Pancreático/tratamento farmacológico , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Recent data have found an overall survival benefit from prostate-directed radiotherapy in patients with low-volume metastatic prostate cancer. Prostate SBRT is an attractive treatment in this setting and may be optimised with MR-guided adaptive treatment. Here, we share our institutional experience delivering stereotactic MR-guided adaptive prostate SBRT (SMART) for patients with low-volume metastatic disease. METHODS: We reviewed patients with low-volume metastatic disease who received prostate SMART from October 2019 to December 2021 on a 0.35T MR-Linac. The cohort included 14 patients. Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed using CTCAE v 5.0. Progression was defined as a change in systemic or hormonal therapy regimen as a result of PSA rise or disease progression. RESULTS: The median follow-up time was 29 months. Seven patients had hormone sensitive prostate cancer and 7 had castrate resistant prostate cancer (CRPC). 13 patients received 36.25 Gy in 5 fractions and one patient received 33 Gy in 5 fractions. At the time of last follow-up, 11 patients had not experienced progression and three patients, all with CRPC, had experienced progression. No patients developed local progression in the prostate after SMART. One patient experienced acute grade 2 urinary toxicity (7%) and no patients experienced acute grade 2 GI toxicity (0%). No grade 3 + acute toxicities were observed. CONCLUSIONS: Prostate SMART was found to be well tolerated and all patients had local control of disease within the prostate at the time of last follow-up. Prostate SMART may represent a low-risk and well-tolerated approach for delivering prostate-directed radiotherapy for patients with limited metastatic disease.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Radiocirurgia , Humanos , Masculino , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Sistema UrogenitalRESUMO
Purpose: To report the utilization of radiation therapy in Syrian refugee patients with prostate cancer residing in Turkey. Methods and materials: A multi-institutional retrospective review including 14 cancer centers in Turkey was conducted to include 137 Syrian refugee patients with prostate cancer treated with radiation therapy (RT). Toxicity data was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Noncompliance was defined as a patient missing two or more scheduled RT appointments. Results: Advanced disease, defined as stage III or IV, was reported in 64.2% of patients while androgen deprivation therapy (ADT) was only administrated to 20% of patients. Conventionally fractionated RT with a median number of 44 fractions was delivered to all patients with curative intent (n = 61) while palliative RT (n = 76) was delivered with a median number of 10 fractions. The acute grade 3-4 toxicity rate for the entire cohort was 16%. Noncompliance rate was 42%. Conclusion: Most Syrian refugee prostate cancer patients presented with advanced disease however ADT was seldom used. Despite the low treatment compliance rate, conventional fractionation was used in all patients. Interventions are critically needed to improve screening and increase the use of standard-of-care treatment paradigms, including hypofractionated RT and ADT.
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Neoplasias da Próstata , Refugiados , Humanos , Masculino , Antagonistas de Androgênios , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , SíriaRESUMO
PURPOSE: There is an unmet need to empirically explore and understand drivers of cancer disparities, particularly social determinants of health. We explored natural language processing methods to automatically and empirically extract clinical documentation of social contexts and needs that may underlie disparities. METHODS: This was a retrospective analysis of 230,325 clinical notes from 5,285 patients treated with radiotherapy from 2007 to 2019. We compared linguistic features among White versus non-White, low-income insurance versus other insurance, and male versus female patients' notes. Log odds ratios with an informative Dirichlet prior were calculated to compare words over-represented in each group. A variational autoencoder topic model was applied, and topic probability was compared between groups. The presence of machine-learnable bias was explored by developing statistical and neural demographic group classifiers. RESULTS: Terms associated with varied social contexts and needs were identified for all demographic group comparisons. For example, notes of non-White and low-income insurance patients were over-represented with terms associated with housing and transportation, whereas notes of White and other insurance patients were over-represented with terms related to physical activity. Topic models identified a social history topic, and topic probability varied significantly between the demographic group comparisons. Classification models performed poorly at classifying notes of non-White and low-income insurance patients (F1 of 0.30 and 0.23, respectively). CONCLUSION: Exploration of linguistic differences in clinical notes between patients of different race/ethnicity, insurance status, and sex identified social contexts and needs in patients with cancer and revealed high-level differences in notes. Future work is needed to validate whether these findings may play a role in cancer disparities.
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Processamento de Linguagem Natural , Neoplasias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Meio Social , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
Background: We assessed radiation treatment (RT) use and complications for unresectable pancreatic cancer in the US, comparing conventionally fractionated (CFRT) and stereotactic body radiation treatment (SBRT) to inform real-world expected outcomes and practice. Material and Methods: We analyzed 5,624 patients with non-metastatic, unresectable pancreatic cancer (2,522 older patients age > 65, diagnosed 2006-2013 in Medicare linked data; and 3,102 younger patients age < 65, diagnosed 2006-2016 in MarketScan data), comparing CFRT vs. SBRT vs. chemotherapy alone. Cochran-Armitage tested temporal trends. Fisher's Exact Test and proportional hazards models compared gastrointestinal (GI) complications. Healthcare payments (Consumer Price Index adjusted to 2015) through 12 months were compared using generalized linear regression models with log link and gamma distribution. Results: RT use declined from 55% to 45% of older patients (2006-2013) and 52% to 47% of younger patients (2006-2016) (Ptrend < 0.001 both). Among RT patients, SBRT use increased to 10% of older patients and 12% of younger patients in the most recent years (Ptrend = 0.04 and < 0.001 respectively). Addition of RT was associated with more frequent GI bleeds, strictures, and fistulas (Δ= +3% to 9% excess events, all P ≤ 0.05). Temporal patterns suggested decreasing complications over time (Ptrend = 0.05 and 0.05 for older and younger patients). Among younger patients, there was no difference in GI complications for SBRT vs. CFRT (P > 0.05, all comparisons). Among older patients, increased complications were seen for SBRT in 1-4 fractions vs. CFRT (P < 0.05), but not SBRT in 5 fractions (P = 0.72). Healthcare payments were greatest for SBRT when compared with CFRT or chemotherapy under US Medicare (P < 0.001) and employer-based insurance (P < 0.001). Conclusion: Real-world treatment has shifted toward more selectivity for RT in unresectable pancreatic cancer. However, SBRT uptake and improving trends in complications profiles represent opportunities to optimize current use and benefit. Findings are applicable to inform future comparative and cost effectiveness models of RT for this disease.
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We developed and implemented an objective toxicity scoring system to be used during endoscopic evaluation of the upper gastrointestinal (GI) tract in order to directly assess changes in toxicity during the radiation treatment of pancreatic cancer. We assessed and validated the upper GI toxicity of 19 locally advanced pancreatic cancer trial patients undergoing stereotactic body radiation therapy (SBRT). Wilcoxon-signed rank tests were used to compare pre- and post-SBRT scores. Comparison of the toxicity scores measured before and after SBRT revealed a mild increase in toxicity in the stomach and duodenum (p < 0.005), with no cases of severe toxicity observed. Kappa and AC1 statistics analysis were used to evaluate interobserver agreement. Our toxicity scoring system was reliable in determining GI toxicity with a good overall interobserver agreement for pre-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.88, p < 0.005) and post-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.76, p < 0.005). The AC1 statistics yielded similar results. With future usage, we hope this scoring system will be a useful tool for objectively and reliably assessing changes in GI toxicity during the treatment of pancreatic cancer and for GI toxicity assessments and comparisons during radiation therapy research trials.
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PURPOSE: Localized pancreatic cancer is commonly treated with stereotactic body radiation therapy (SBRT), which often requires the placement of fiducial markers. We compared the clinical outcomes of patients with and without fiducial markers. METHODS AND MATERIALS: We retrospectively collected data on patients with pancreatic cancer treated with neoadjuvant SBRT at a single institution. Patients were divided into 2 groups based on the placement of a fiducial marker. Local recurrence was the primary outcome. Time to event endpoints were analyzed using COX regression. RESULTS: We included 96 patients with unresectable pancreatic cancer: 46 patients (47.9%) did not have a fiducial marker, and 50 patients (52.1%) had a fiducial placed. Patients in the fiducial group were older and had more locally advanced pancreatic cancer compared with those who did not have a fiducial placed. Most patients in both groups (92.7%) received chemotherapy before SBRT treatment. SBRT was delivered to a median of 36 Gy over 5 fractions in the no-fiducial group, and 38 Gy over 5 fractions in the fiducial group. At a median follow-up of 20 months, local recurrence was similar irrespective of fiducial placement (adjusted hazard ratio [aHR] 0.6, 95% CI 0.3-1.3, P = .59). Furthermore, no difference in overall survival was noted between the 2 groups (aHR 0.8, 95% CI 0.3-1.9, P = .65). In patients who eventually underwent surgery post-SBRT, no difference in surgical margins (P = .40) or lymphovascular invasion (P = .76) was noted between the 2 groups. No patient developed acute pancreatitis after fiducial placement. CONCLUSIONS: Our data suggest that the use of fiducial markers does not negatively affect clinical outcomes in patients with localized pancreatic cancer. Prospective confirmation of our results is still needed.
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PURPOSE: Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa. METHODS AND MATERIALS: A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/ß= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting. RESULTS: After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%. CONCLUSIONS: Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.
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Neoplasias Pancreáticas/radioterapia , Radiocirurgia/métodos , Relação Dose-Resposta à Radiação , Humanos , Estimativa de Kaplan-Meier , Funções Verossimilhança , Modelos Lineares , Modelos Biológicos , Modelos Teóricos , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/estatística & dados numéricos , Probabilidade , Hipofracionamento da Dose de Radiação , Radiocirurgia/efeitos adversos , Radioterapia Adjuvante/métodos , Resultado do TratamentoRESUMO
PURPOSE: Preoperative chemoradiation is being currently evaluated in 2 randomized international trials. However, chemoradiation for gastric cancer can be associated with relatively high rates of acute toxicity. We compared rates of toxicity, toxicity-related events, and oncologic outcomes in patients treated with intensity modulated radiation therapy (IMRT) and those treated with 3-dimensional conformal radiation therapy (3DCRT). METHODS AND MATERIALS: We retrospectively reviewed records of 202 patients with consecutive gastric cancer treated with preoperative intent radiation therapy at our institution from 1998 to 2018. Patients with gastroesophageal junction involvement and those with metastatic disease were excluded. Eighty-two patients received 3DCRT, and 120 patients received IMRT. The median radiation dose was 45 Gy, and 99% received concurrent chemotherapy. RESULTS: There were no significant differences between the 3DCRT and IMRT groups regarding sex, race, histology, tumor location, histology, or nodal stage. The rate of grade 3 to 4 acute toxicity was significantly lower in patients treated with IMRT compared with 3DCRT (49% vs 70%, P = .004). The composite rate of toxicity-related events (hospitalization, feeding tube use, intravenous rehydration, or radiation therapy breaks) was also significantly lower in patients treated with IMRT compared with 3DCRT (56% vs 85%, P <.001). In addition, 68% of patients who received IMRT and 73% of patients who received 3DCRT underwent subsequent surgical resection (P = .245). Among patients who underwent surgery, the 3-year overall survival rates were not significantly different between those treated with IMRT and 3DCRT (71% vs 69%, P = .786). Patients receiving IMRT had a significantly higher absolute nadir lymphocyte count compared with patients receiving 3DCRT (median, 0.21 vs 0.16 K/UL; P = .047). CONCLUSIONS: Our study suggests that IMRT might significantly reduce rates of grade 3 to 4 acute toxicity and toxicity-related events compared with 3DCRT, with no significant difference in oncologic outcomes. IMRT is an appropriate and possibly preferable radiation modality in patients treated with preoperative chemoradiation for gastric cancer.
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Landmark investigation two decades ago demonstrated sex-based disparities among participants in cancer cooperative group trials. Although federal efforts have aimed to improve representation of female patients in government-sponsored research, less is known about sex disparities in the broader landscape of modern oncologic randomized controlled trials. Using ClinicalTrials.gov, we identified randomized controlled trials related to colorectal or lung cancer (the two most common non-sex-specific disease sites). Among the 147 included trials, the proportion of female patients enrolled on trial was on average 6.8% (95% confidence interval = -8.8% to -4.9%) less than the proportion of female patients in the population by disease site (P < .001). Whereas no statistically significant underrepresentation of women was noted within the 26 cooperative group trials, sex disparities were markedly heightened for the 121 noncooperative-group-sponsored trials. Furthermore, underrepresentation of women did not improve with time. Future efforts should therefore focus on addressing these pervasive sex-based enrollment disparities beyond cooperative group trials alone.