Immunotherapy can be an effective treatment for metastatic cancer, but a significant subpopulation will not respond, likely due to the lack of antigenic mutations or the immune-evasive properties of ...cancer. Likewise, radiation therapy (RT) is an established cancer treatment, but local failures still occur. Clinical observations suggest that RT may expand the therapeutic reach of immunotherapy. We examine the immunobiologic and clinical rationale for combining RT and immunotherapy, two modalities yet to be used in combination in routine practice. Preclinical data indicate that RT can potentiate the systemic efficacy of immunotherapy, while activation of the innate and adaptive immune system can enhance the local efficacy of RT.
Opinion statement
High-risk localized prostate cancer is a challenging clinical entity to treat, with heterogeneous responses to an evolving array of multidisciplinary treatment approaches. In ...addition, this disease state is growing in incidence due to a variety of factors, including shifting recommendations that discouraged routine prostate cancer screening. Current guidelines now incorporate an informed decision-making process for prostate cancer screening and evaluation. More work is underway to improve targeted screening for certain at-risk populations and to implement greater personalization in the use of diagnostic tools. Once diagnosed with high-risk localized disease, a multimodality treatment paradigm is warranted. Radiation—in its various forms and combinations—plays a large and continually evolving role in the management of high-risk prostate cancer, yet treatment outcomes are still suboptimal. There is a growing need to improve upon current treatment approaches, and better personalize a particular treatment recommendation based on both tumor and patient characteristics, as well as patient preference and goals of therapy. Given that treatment generally requires more than one therapy, there are notable implications on long-term quality of life, especially with respect to overlapping and cumulative side effects of local and systemic therapies, respectively. The desire for aggressive therapy to optimize cancer control outcomes must be weighed against the risk of morbidities and overtreatment and discussed with each patient so that an informed decision about treatment and care can be determined. High-level evidence to support treatment recommendations, where available, is critical for a data-driven and tailored approach to address all goals of care.
There is little consensus regarding preoperative magnetic resonance imaging (MRI) in breast cancer (BC). We examined the association between preoperative MRI and local recurrence (LR) as primary ...outcome, as well as distant recurrence (DR), in patients with BC.
An individual person data (IPD) meta-analysis, based on preoperative MRI studies that met predefined eligibility criteria, was performed. Survival analysis (Cox proportional hazards modeling) was used to investigate time to recurrence and to estimate the hazard ratio (HR) for MRI. We modeled the univariable association between LR (or DR) and MRI, and covariates, and fitted multivariable models to estimate adjusted HRs. Sensitivity analysis was based on women who had breast conservation with radiotherapy.
Four eligible studies contributed IPD on 3,180 affected breasts in 3,169 subjects (median age, 56.2 years). Eight-year LR-free survival did not differ between the MRI (97%) and no-MRI (95%) goups (P = .87), and the multivariable model showed no significant effect of MRI on LR-free survival: HR for MRI (versus no-MRI) was 0.88 (95% CI, 0.52 to 1.51; P = .65); age, margin status, and tumor grade were associated with LR-free survival (all P < .05). HR for MRI was 0.96 (95% CI, 0.52 to 1.77; P = .90) in sensitivity analysis. Eight-year DR-free survival did not differ between the MRI (89%) and no-MRI (93%) groups (P = .37), and the multivariable model showed no significant effect of MRI on DR-free survival: HR for MRI (v no-MRI) was 1.18 (95% CI, 0.76 to 2.27; P = .48) or 1.31 (95% CI, 0.76 to 2.27; P = .34) in sensitivity analysis.
Preoperative MRI for staging the cancerous breast does not reduce the risk of LR or DR.
Moderately hypofractionated radiation therapy represents an effective treatment for localized prostate cancer (PC). Although large randomized trials have reported the efficacy of photon-based ...hypofractionated therapy, hypofractionated proton therapy (HFPT) has not been extensively studied. This study was performed to determine the clinical and patient-reported outcomes for patients with PC treated with HFPT.
Between 2010 and 2017, 184 men were enrolled on a trial of 70 Gy in 28 fractions of HFPT for low- to intermediate-risk PC. Acute and late toxicity was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Patient-reported outcomes were measured by International Prostate Symptom Score, International Index of Erectile Function Questionnaire, and Expanded Prostate Cancer Index Composite scores.
Median follow-up was 49.2 months. Enrolled patients had low-risk (n = 18), favorable intermediate-risk (n = 78), and unfavorable intermediate-risk (n = 88) PC. Four-year rates of biochemical-clinical failure-free survival were 93.5% (95% confidence interval, 89%-98%), 94.4% (89%-100%), 92.5% (86%-100%), and 93.8% (88%-100%) in the overall group and the low-risk, favorable intermediate-risk, and unfavorable intermediate-risk cohorts, respectively (log-rank P > .4). The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic toxicities were 3.8% and 12.5%, respectively. The 4-year incidence of late grade 2 or higher urologic and GI toxicity was 7.6% (4%-13%) and 13.6% (9%-20%), respectively. One late grade 3 GI toxicity was reported. All late toxicities were transient. Patient-reported International Prostate Symptom, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite scores had no significant long-term changes after completion of HFPT (Supplementary Table 1, available at https://doi.org/10.1016/j.ijrobp.2019.05.069).
HFPT is associated with low rates of toxicity and does not appear to negatively affect 4-year patient reported urinary and bowel health. Further comparative analyses are warranted to better understand differences between proton and photon HFRT.
Hospitals account for approximately 6% of United States' gross domestic product. We examined the association between hospital competition and outcomes in elderly with localized prostate cancer (PCa). ...We also assessed if race moderated this association.
Retrospective study using Surveillance, Epidemiology, and End Results (SEER) - Medicare database. Cohort included fee-for-service, African American and white men aged ≥ 66, diagnosed with localized PCa between 1998 and 2011 and their claims between 1997 and 2016. We used Hirschman-Herfindahl index (HHI) to measure of hospital competition. Outcomes were emergency room (ER) visits, hospitalizations, Medicare expenditure and mortality assessed in acute survivorship phase (two years post-PCa diagnosis), and long-term mortality. We used Generalized Linear Models for analyzing expenditure, Poisson models for ER visits and hospitalizations, and Cox models for mortality. We used propensity score to minimize bias.
Among 253,176 patients, percent change in incident rate of ER visit was 17% higher for one unit increase in HHI (IRR: 1.17, 95% CI: 1.15-1.19). Incident rate of ER was 24% higher for whites and 48% higher for African Americans. For one unit increase in HHI, hazard of short-term all-cause mortality was 7% higher for whites and 11% lower for African Americans. The hazard of long-term all-cause mortality was 10% higher for whites and 13% higher for African Americans.
Lower hospital competition was associated with impaired outcomes of localized PCa care. Magnitude of impairment was higher for African Americans, compared to whites. Future research will explore process through which competition affects outcomes and racial disparity.
Health disparities in prostate cancer (PC) are thought to reflect the complex interplay of socioeconomics, environment and biology. The potential impact of beliefs and perceptions about PC among ...Black and Latino populations on clinical disparities are not well understood. This qualitative study was conducted to assess current prevalent and pervasive stigma, beliefs and perceptions regarding PC among Blacks and Latinos living in a large metropolitan area, thereby identifying potentially modifiable barriers to care.
Qualitative data were collected through four separate focus groups of self-identified Black and Latino adult men and women living in Philadelphia to better understand their perceptions of PC diagnosis, screening and treatment. Each focus group was single-sex and conducted by racial/ethnic group in order to assess possible differences in beliefs about PC based on gender and racial/ethnic affiliation. Audio recordings were transcribed verbatim by trained research assistants and qualitative data analysis was conducted using modified grounded theory.
There were a total of 34 participants: 19 Hispanics/Latinos and 15 Blacks, with equal numbers of men and women (n=17). Median age was 57 years (range: 18 to 85 years). Dominant themes that emerged with respect to PC diagnosis included the stigma surrounding this condition and the perceived role of an "unhealthy lifestyle" and certain sexual behaviors as risk factors for PC development. While the majority of participants acknowledged the importance of PC screening and early detection, discussion centered around the barriers to both the interest in seeking medical care and the likelihood of securing it. These barriers included misunderstanding of PC etiology, distrust of the medical profession, and financial/access limitations. Men expressed substantial confusion about PC screening guidelines. In the Black female group, the role of faith and religion in the course of disease was a major theme. Both Black and Latina females discussed the role of fear and avoidance around PC screening and treatment, as well as the prevalence of misinformation about PC in their familial and social communities.
Black and Latino focus groups revealed the existence of cultural beliefs, misunderstandings and fears pertaining to PC which could influence health-related behaviors. Some themes were common across groups; others suggested racial and gender predilections. Future targeted efforts focused on directly addressing prevalent misperceptions among underserved communities in urban settings could help to improve health literacy and equity in PC outcomes in these populations.
PDF
