Achieving flexible competence: bridging the investment dichotomy between infectious diseases and cancer.

Today's global health challenges in underserved communities include the growing burden of cancer and other non-communicable diseases (NCDs); infectious diseases (IDs) with epidemic and pandemic potential such as COVID-19; and health effects from catastrophic 'all hazards' disasters including natural, industrial or terrorist incidents. Healthcare disparities in low-income and middle-income countries and in some rural areas in developed countries make it a challenge to mitigate these health, socioeconomic and political consequences on our globalised society. As with IDs, cancer requires rapid intervention and its effective medical management and prevention encompasses the other major NCDs. Furthermore, the technology and clinical capability for cancer care enables management of NCDs and IDs. Global health initiatives that call for action to address IDs and cancer often focus on each problem separately, or consider cancer care only a downstream investment to primary care, missing opportunities to leverage investments that could support broader capacity-building. From our experience in health disparities, disaster preparedness, government policy and healthcare systems we have initiated an approach we call flex-competence which emphasises a systems approach from the outset of program building that integrates investment among IDs, cancer, NCDs and disaster preparedness to improve overall healthcare for the local community. This approach builds on trusted partnerships, multi-level strategies and a healthcare infrastructure providing surge capacities to more rapidly respond to and manage a wide range of changing public health threats.

The international cancer expert corps: a unique approach for sustainable cancer care in low and lower-middle income countries.

The growing burden of non-communicable diseases including cancer in low- and lower-middle income countries (LMICs) and in geographic-access limited settings within resource-rich countries requires effective and sustainable solutions. The International Cancer Expert Corps (ICEC) is pioneering a novel global mentorship-partnership model to address workforce capability and capacity within cancer disparities regions built on the requirement for local investment in personnel and infrastructure. Radiation oncology will be a key component given its efficacy for cure even for the advanced stages of disease often encountered and for palliation. The goal for an ICEC Center within these health disparities settings is to develop and retain a high-quality sustainable workforce who can provide the best possible cancer care, conduct research, and become a regional center of excellence. The ICEC Center can also serve as a focal point for economic, social, and healthcare system improvement. ICEC is establishing teams of Experts with expertise to mentor in the broad range of subjects required to establish and sustain cancer care programs. The Hubs are cancer centers or other groups and professional societies in resource-rich settings that will comprise the global infrastructure coordinated by ICEC Central. A transformational tenet of ICEC is that altruistic, human-service activity should be an integral part of a healthcare career. To achieve a critical mass of mentors ICEC is working with three groups: academia, private practice, and senior mentors/retirees. While in-kind support will be important, ICEC seeks support for the career time dedicated to this activity through grants, government support, industry, and philanthropy. Providing care for people with cancer in LMICs has been a recalcitrant problem. The alarming increase in the global burden of cancer in LMICs underscores the urgency and makes this an opportune time fornovel and sustainable solutions to transform cancer care globally.

Aspirin improves outcome in high risk prostate cancer patients treated with radiation therapy.

PURPOSE: High-risk prostate cancer (PC) has poor outcomes due to therapeutic resistance to conventional treatments, which include prostatectomy, radiation, and hormone therapy. Previous studies suggest that anticoagulant (AC) use may improve treatment outcomes in PC patients. We hypothesized that AC therapy confers a freedom from biochemical failure (FFBF) and overall survival (OS) benefit when administered with radiotherapy in patients with high-risk PC. MATERIALS AND METHODS: Analysis was performed on 74 high-risk PC patients who were treated with radiotherapy from 2005 to 2008 at UT Southwestern. Of these patients, 43 were on AC including aspirin (95.6%), clopidogrel (17.8%), warfarin (20%), and multiple ACs (31.1%). Associations between AC use and FFBF, OS, distant metastasis, and toxicity were analyzed. RESULTS: Median follow-up was 56.6 mo for all patients. For patients taking any AC compared with no AC, there was improved FFBF at 5 years of 80% vs. 62% (P = 0.003), and for aspirin the FFBF was 84% vs. 65% (P = 0.008). Aspirin use was also associated with reduced rates of distant metastases at 5 years (12.2% vs. 26.7%, P = 0.039). On subset analysis of patients with Gleason score (GS) 9-10 histology, aspirin resulted in improved 5-year OS (88% vs. 37%, P = 0.032), which remained significant on multivariable analysis (P<0.05). CONCLUSIONS: AC use was associated with a FFBF benefit in high-risk PC which translated into an OS benefit in the highest risk PC patients with GS 9-10, who are most likely to experience mortality from PC. This hypothesis-generating result suggests AC use may represent an opportunity to augment current therapy.

A comparison of radiographic techniques and electromagnetic transponders for localization of the prostate.

BACKGROUND: The aim of this study is to compare three methodologies of prostate localization and to determine if there are significant differences in the techniques. METHODS: Daily prostate localization using cone beam CT or orthogonal kV imaging has been performed at UT Southwestern Medical Center since 2006. Prostate patients are implanted with gold seeds, which are matched with the planning CT or DRR before treatment. More recently, a technology using electromagnetic transponders implanted within the prostate was introduced into our clinic (Calypso®). With each technology, patients are localized initially using skin marks and the room lasers. In this study, patients were localized with Calypso and either CBCT or kV orthogonal images in the same treatment session, allowing a direct comparison of the technologies. Localization difference distributions were determined from the difference in the offsets determined by CBCT/kV imaging and Calypso. CBCT-Calypso and kV imaging-Calypso localization data were summarized from over 900 and 250 fractions each, respectively. The Wilcoxon signed rank test is used to determine if the localization differences are statistically significant. We also calculated Pearson's product-moment correlation coefficient (R2) to determine if there is a linear relationship between the shifts determined by Calypso and the radiographic techniques. RESULTS: The differences between CBCT-Calypso and kV imaging-Calypso localizations are -0.18 ± 2.90 mm, -0.79 ± 2.18 mm, -0.01 ± 1.20 mm and -0.09 ± 1.40 mm, 0.48 ± 1.50 mm, 0.08 ± 1.04 mm, respectively, in the AP, SI, and RL directions. The Pearson product-moment correlation coefficients for the CBCT-Calypso shifts were 0.71, 0.92 and 0.88 and for the OBI-Calypso comparison were 0.95, 0.89 and 0.85. The percentage of localization differences that were less than 3 mm were 86.1%, 84.5% and 96.0% for the CBCT-Calypso comparison and 95.8%, 94.3% and 97% for the kV OBI-Calypso comparison. No trends were observed in the Bland-Altman analysis. CONCLUSIONS: Localization of the prostate using electromagnetic transponders agrees well with radiographic techniques and each technology is suitable for high precision radiotherapy. This study finds that there is more uncertainty in CBCT localization of the prostate than in 2D orthogonal imaging, but the difference is not clinically significant.

Robotically guided radiosurgery for children.

BACKGROUND: A robotically guided linear accelerator has recently been developed which provides frameless radiosurgery with high precision. Potential advantages for the pediatric population include the avoidance of the cognitive decline associated with whole brain radiotherapy, the ability to treat young children with thin skulls unsuitable for frame-based methods, and the possible avoidance of general anesthesia. We report our experience with this system (the "Cyberknife") in the treatment of 21 children. PROCEDURES: Cyberknife radiosurgery was performed on 38 occasions for 21 patients, age ranging from 8 months to 16 years (7.0 +/- 5.1 years), with tumors considered unresectable. Three had pilocytic astrocytomas, two had anaplastic astrocytomas, three had ependymomas (two anaplastic), four had medulloblastomas, three had atypical teratoid/rhabdoid tumors, three had craniopharyngiomas, and three had other pathologies. The mean target volume was 10.7 +/- 20 cm(3), mean marginal dose was 18.8 +/- 8.1 Gy, and mean follow-up is 18 +/- 11 months. Twenty-seven (71%) of the treatments were single-shot and eight (38%) patients did not require general anesthesia. RESULTS: Local control was achieved in the patients with pilocytic and anaplastic astrocytoma, three of the patients with medulloblastoma, and the three with craniopharyngioma, but not for those with ependymoma. Two of the patients with rhabdoid tumors are alive 16 and 35 months after this diagnosis. There have been no procedure related deaths or complications. CONCLUSION: Cyberknife radiosurgery can be used to achieve local control for some children with CNS tumors without the need for rigid head fixation.

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

CONTEXT: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. OBJECTIVE: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. DESIGN, SETTING, AND PATIENTS: Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. MAIN OUTCOME MEASURE: Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. RESULTS: Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. CONCLUSIONS: Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.

Salvage radiotherapy for biochemical failure of radical prostatectomy: a single-institution experience.

OBJECTIVES: To review the efficacy of salvage radiotherapy (RT), to treat elevated prostate-specific antigen (PSA) levels for presumed local recurrence of prostatic adenocarcinoma after retropubic prostatectomy, and identify the factors that may predict for successful treatment. METHODS: Fifty-one patients with hormonally naive pT2-3N0-1M0 prostate cancer were treated with RT for locally persistent or recurrent disease. The patients received a median dose of 65.7 Gy (range 61.2 to 72.3) to the prostate bed. Successfully treated patients had undetectable PSA levels; the endpoint of the study was biochemical failure. RESULTS: The median follow-up was 3.8 years; 42 of 51 patients had at least 2 years of follow-up. Twenty-three patients (45%) were biochemically free of disease. The estimated biochemically free of disease rate at 3 and 5 years was 56% and 16%, respectively. Whether the patients were treated for persistently elevated PSA levels or for rising PSA levels from undetectable levels after retropubic prostatectomy, their PSA values were equally likely to drop to undetectable levels (65%). Univariate analysis demonstrated two factors that significantly predicted for successful salvage treatment: the absence of seminal vesicle invasion and the absence of lymphovascular invasion. A pretreatment PSA level less than 0.425 ng/mL trended toward statistical significance (P = 0.059). Only seminal vesicle invasion maintained significance on multivariate analysis. The RT was well tolerated, and the gastrointestinal and genitourinary toxicity was largely Radiation Therapy Oncology Group grade 1. CONCLUSIONS: Salvage RT is moderately effective in treating patients with locally persistent or recurrent prostate adenocarcinoma. Seminal vesicle invasion and lymphovascular invasion predicted for unsuccessful treatment.