Addressing challenges in low-income and middle-income countries through novel radiotherapy research opportunities.

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.

Proximity to Radiotherapy Center, Population, Average Income, and Health Insurance Status as Predictors of Cancer Mortality at the County Level in the United States.

PURPOSE: Sufficient radiotherapy (RT) capacity is essential to delivery of high-quality cancer care. However, despite sufficient capacity, universal access is not always possible in high-income countries because of factors beyond the commonly used parameter of machines per million people. This study assesses the barriers to RT in a high-income country and how these affect cancer mortality. METHODS: This cross-sectional study used US county-level data obtained from Center for Disease Control and Prevention and the International Atomic Energy Agency Directory of Radiotherapy Centres. RT facilities in the United States were mapped using Geographic Information Systems software. Univariate analysis was used to identify whether distance to a RT center or various socioeconomic factors were predictive of all-cancer mortality-to-incidence ratio (MIR). Significant variables (P ≤ .05) on univariate analysis were included in a step-wise backward elimination method of multiple regression analysis. RESULTS: Thirty-one percent of US counties have at least one RT facility and 8.3% have five or more. The median linear distance from a county's centroid to the nearest RT center was 36 km, and the median county all-cancer MIR was 0.37. The amount of RT centers, linear accelerators, and brachytherapy units per 1 million people were associated with all-cancer MIR (P < .05). Greater distance to RT facilities, lower county population, lower average income per county, and higher proportion of patients without health insurance were associated with increased all-cancer MIR (R-squared, 0.2113; F, 94.22; P < .001). CONCLUSION: This analysis used unique high-quality data sets to identify significant barriers to RT access that correspond to higher cancer mortality at the county level. Geographic access, personal income, and insurance status all contribute to these concerning disparities. Efforts to address these barriers are needed.

Incidence and extent of disease progression on MRI between surgery and initiation of radiotherapy in glioblastoma patients.

Background: A post-operative MRI (MRIpost-op) performed within 72 h is routinely used for radiation treatment planning in glioblastoma (GBM) patients, with radiotherapy starting about 4-6 weeks after surgery. Some patients undergo an additional pre-radiotherapy MRI (MRIpre-RT) about 2-6 weeks after surgery. We sought to analyze the incidence of rapid early progression (REP) between surgery and initiation of radiotherapy seen on MRIpre-RT and the impact on radiation target volumes. Methods: Patients with GBM diagnosed between 2018 and 2020 who had an MRIpost-op and MRIpre-RT were retrospectively identified. Criteria for REP was based on Modified RANO criteria. Radiation target volumes were created and compared using the MRIpost-op and MRIpre-RT. Results: Fifty patients met inclusion criteria. The median time between MRIpost-op and MRIpre-RT was 26 days. Indications for MRIpre-RT included clinical trial enrollment in 41/50 (82%), new symptoms in 5/50 (10%), and unspecified in 4/50 (8%). REP was identified in 35/50 (70%) of patients; 9/35 (26%) had disease progression outside of the MRIpost-op-based high dose treatment volumes. Treatment planning with MRIpost-op yielded a median undertreatment of 27.1% of enhancing disease and 11.2% of surrounding subclinical disease seen on MRIpre-RT. Patients without REP had a 38% median volume reduction of uninvolved brain if target volumes were planned with MRIpre-RT. Conclusion: Given the incidence of REP and its impact on treatment volumes, we recommend using MRIpre-RT for radiation treatment planning to improve coverage of gross and subclinical disease, allow for early identification of REP, and decrease radiation treatment volumes in patients without REP.

Radiation Therapy in Conjunction With Surgical Stabilization of Impending or Pathologic Fractures Secondary to Metastasis: Is There a Difference Between Single and Multifraction Regimens?

PURPOSE: Patients who undergo surgical stabilization for impending or pathologic fractures secondary to metastasis are often treated with radiation therapy to the involved site. We sought to retrospectively analyze outcomes from single versus multifraction regimens of radiation therapy in this setting. METHODS AND MATERIALS: From our institutional radiation database, we identified 87 patients between 2004 and 2016 who had an impending or pathologic fracture from metastatic disease and who underwent surgical fixation in conjunction with either neoadjuvant (within 5 weeks before surgery) or adjuvant (within 10 weeks after surgery) radiation therapy, representing 99 total treatment sites. Patients were included on the basis of intention to treat with bimodality therapy. Baseline patient characteristics were compared using 2-sided t tests and Fisher's exact tests. Cumulative incidence of local failure, reirradiation, and reoperation were calculated using the Fine-Gray method for competing risks. Freedom from complication was calculated using the Kaplan-Meier method. RESULTS: Baseline characteristics between the single (n = 52) and multifraction (n = 47) cohorts were similar with the exception of higher rates of synchronous bony metastasis (83% vs 60%, P = .01) and female patients (71% vs 43%, P = .004) in the single fraction cohort. There was no significant difference in overall survival between treatment groups. After a median follow-up of 13 months, there was no significant difference in the single and multifraction cohorts, respectively, in the 1-year cumulative incidence rates of local failure (4% vs 7%, P = .58), reirradiation (5% vs 4%, P = .95), reoperation (4% vs 0%, P = .30), or 1-year freedom from complication (90% vs 95%, P = .40). CONCLUSIONS: This is the first study comparing outcomes between single and multifraction radiation therapy in conjunction with surgical stabilization of an impending or pathologic fracture. We found no difference in outcomes between single and multifraction regimens in this setting. Given these findings, single fraction perioperative radiation therapy may be a viable treatment option in appropriately selected patients pending prospective validation of these findings.

Investigating association of perineural invasion on prostate biopsy with Gleason score upgrading at prostatectomy: A multi-institutional analysis.

BACKGROUND: The significance of perineural invasion (PNI) in prostate cancer (PC) is unclear. A recent report of patients with pT2N0R0 PC found that PNI at prostatectomy was independently associated with higher Gleason score and more diffuse prostatic disease. We aimed to test our hypothesis that PNI on prostate biopsy in pT2N0R0 patients is associated with increased Gleason score upgrading at prostatectomy. METHODS: We identified 2892 patients status post prostatectomy with pT2N0R0 PC from three institutions, diagnosed between 1 January 2008 and 31 December 2014. Multivariable logistic regression (MVA) was used to evaluate the association between prostate biopsy PNI status and surgical Gleason upgrading, while controlling for potential confounders. RESULTS: Of the 2892 patients identified, 14% had PNI on biopsy, of whom 21% had surgical Gleason upgrading, while 28% without PNI on biopsy had such upgrading (P < .01). On MVA, the odds ratio (OR) of surgical Gleason upgrading for patients with biopsy PNI relative to patients without biopsy PNI was 0.69 (P < .01). The variables associated with surgical Gleason upgrading were age ≤60 years (OR 1.22, P = .02) and preoperative PSA >4 ng/mL (OR 1.26, P = .02). CONCLUSIONS: In post-prostatectomy patients with favorable-risk PC, PNI on prostate biopsy was not associated with surgical Gleason score upgrading. This may be due to the association of PNI with more diffuse disease, leading to increased biopsy tumor yield and grading accuracy. These findings suggest that in this setting, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision-making for men debating active surveillance, radiation, and surgery.

The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients With pT2N0R0 Prostate Cancer? A Multi-Institutional Study.

PURPOSE: Perineural invasion (PNI) is a histologic feature that is present in as many as 84% of patients with prostate cancer. The prognostic significance of PNI is controversial, with recent studies yielding contradictory results. This study aims to assess whether PNI, on the surgical pathology of patients with pT2N0M0 disease and with negative surgical margins, is an independent prognostic indicator of the risk of biochemical recurrence. METHODS AND MATERIALS: We identified 1549 patients who received a diagnosis of margin-negative pT2N0M0 prostate cancer at 3 separate institutions between January 1, 2008 and December 31, 2014. We reviewed the electronic medical records of these patients and collected clinical and histologic data. A multivariable analysis was performed to assess the association between PNI and biochemical recurrence. RESULTS: Of the 1549 patients identified, 936 (60.4%) had PNI and 96 (6.2%) had biochemical recurrence. The median time until recurrence was 16 months. The median follow-up in patients without recurrence was 26.5 months. PNI was associated with pT2c disease. The proportion of patients with pT2c was 89% in patients with PNI compared with 79% in patients without PNI (P < .001). PNI was also associated with a higher surgical Gleason score (of those with vs without PNI, 21% vs 50% had Gleason score 3 + 3; 62% vs 41% had a Gleason score 3 + 4, 12% vs 5% had a Gleason score 4 + 3; and 5% vs 3% had a Gleason score 8-10; P < .001). On univariate analysis, patients with PNI appeared to be more likely to have disease recurrence (hazard ratio: 1.7; 95% confidence interval, 1.1-2.6; P = .015). However, after adjusting for other variables, there was not a significant association between PNI and recurrence (hazard ratio: 1.1; 95% confidence interval, 0.70-1.8: P = .65). CONCLUSIONS: We found that PNI was not an independent indicator of the risk of biochemical recurrence. Instead, PNI may be an indicator of unfavorable histology such as a high Gleason score or diffuse disease within the prostate in pT2N0 patients.

Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults.

OBJECTIVES: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger. MATERIALS AND METHODS: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts. RESULTS: Median patient age was 35 years (range, 19-40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001). CONCLUSION: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.

Using hospital medical record data to assess the accuracy of the SEER Los Angeles Cancer Surveillance Program for initial treatment of prostate cancer: a small pilot study.

PURPOSE: Treatment information from the Surveillance, Epidemiology, and End Result Program (SEER) cancer registries is increasingly being used for population-based cancer research; however, it may be incomplete for outpatient procedures and is not quality controlled. We sought to validate SEER information on initial treatment of prostate cancer by comparison to electronic medical record (EMR) review. METHODS: Patients diagnosed with prostate cancer between 1 January 2010 and 31 December 2014 in Los Angeles County who received treatment at our institution within 6 months of diagnosis were identified from the SEER registry. We reviewed the hospital EMR for these patients and identified initial treatment received within 6 months of diagnosis. We compared data reported to SEER data to our re-abstracted hospital EMR data (defined as the gold standard) to identify the completeness of SEER treatment data (sensitivity) and the accuracy of the SEER information (positive predictive value). RESULTS: Based on 266 eligible patients, SEER's sensitivity in capturing initial treatment was 95.9% (118/123) for prostatectomy, 95.8% (69/72) for no treatment, 87.5% (21/24) for radiation therapy, 68.3% (28/41) for active surveillance or watchful waiting, and 50.0% (2/4) for cryosurgery. The SEER positive predictive value was 100% for radiation therapy and cryosurgery, 97.5% (118/121) for radical prostatectomy, 82.3% (28/34) for active surveillance or watchful waiting, and 78.4% (69/88) for no treatment. CONCLUSION: The SEER data were highly sensitive and has a high positive predictive value for surgery and radiation therapy but underreported use of active surveillance. These results may assist researchers in understanding the strengths and weaknesses of using SEER prostate cancer treatment data.

Active Surveillance for Prostate Cancer: Are We Failing Latino Patients at a Large Safety Net Hospital?

INTRODUCTION: Active surveillance (AS) is one recommended option for low-risk prostate cancer and involves close follow-up and monitoring. Our objective was to determine whether non-clinical trial patients adhere to AS protocols and how many are lost to follow-up (LTFU). PATIENTS AND METHODS: Retrospective chart review was performed for patients with nonmetastatic prostate cancer who initiated AS at Los Angeles County Hospital (LAC) and University of Southern California Norris Comprehensive Cancer Center (Norris) between January 1, 2008, and January 1, 2015. Competing-risks regression analyses examined the difference in LTFU rates of AS patients in the 2 institutions and examined the association between LTFU and patient characteristics. We used California Cancer Registry data to verify if patients LTFU were monitored and/or treated at other LAC medical facilities. RESULTS: We found 116 patients at LAC and 98 at Norris who met the AS criteria for this study. Patients at LAC and Norris had similar tumor characteristics but differed in median income, race, primary language spoken, distance residing from hospital, and socioeconomic status (SES). LTFU was significantly different between the institutions: 57 ± 7% at LAC and 32 ± 6% at Norris at 5 years (P < .001). By multivariable analysis, the main determinant of LTFU was SES (P = .045). By 5 years, the chance of an LAC patient remaining on AS was 8 ± 6% compared to 20 ± 6% for a Norris patient (P < .001). CONCLUSION: Successful AS implementation relies on patient follow-up. We found that patients on AS from lower SES strata are more often LTFU. Identifying barriers to follow-up and compliance among low SES patients is critical to ensure optimal AS.