Human papillomavirus-positive oropharynx cancer incidence has increased rapidly in cohorts of US white men born during the 1930s to 1950s. It is unknown how the trajectory of the oropharynx cancer ...epidemic may be changing in the United States.
Using US cancer registry information, we investigated whether increases in oropharynx cancer have continued into recent birth cohorts and forecasted the future burden across age, sex, and race/ethnicity subgroups. Log-linear Joinpoint regression and age-period-cohort models were used to evaluate incidence trends during 1992 to 2015 and projections through 2029.
Among white men, oropharynx cancer incidence increased rapidly in individuals born during 1939 to 1955 (5.3% per 2-year birth cohort; 95% CI, 4.8% to 5.7%), but this rate of increase significantly moderated in individuals born during 1955 to 1969 (1.7% per 2-year birth cohort; 95% CI, 1.0% to 2.4%). Should these birth-cohort trends continue, from 2016 to 2029 we forecast that incidence will increase dramatically in older white men 65 to 74 years of age (from 40.7 to 71.2 per 100,000) and 75 to 84 years of age (from 25.7 to 50.1 per 100,000), moderately in white men 55 to 64 years of age (from 40.3 to 52.0 per 100,000), and remain stable in white men 45 to 54 years of age (approximately 18 per 100,000). Accounting for population growth, we project an increase in annual number of cases in the United States from 20,124 (95% CI, 19,779 to 20,469) in 2016 to 30,629 (95% CI, 29,413 to 31,845) in 2029, primarily driven by older individuals (age ≥ 65 years; from 7,976 95% CI, 7,782 to 8,172 to 18,072 95% CI, 17,271 to 18,895) and white men (from 14,453 95% CI, 14,142 to 14,764 to 22,241 95% CI, 21,119 to 23,364).
The exponential increase in oropharynx cancer incidence in young white US men has ebbed, and modest increases are occurring/anticipated in cohorts born after 1955. Continued strong increases in incidence in cohorts born before 1955, and an approximate 50% increase in size of the US population age 65 years or older through 2029, portend a substantial shift in burden to elderly white men.
Purpose Current staging systems for oral cavity cancers incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigated the ...independent impact of numerical metastatic LN burden on survival. Methods Adult patients with oral cavity squamous cell carcinoma undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004 and 2013. A neck dissection of a minimum of 10 LNs was required. Multivariable models were constructed to assess the association between the number of metastatic LNs and survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Results Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs (HR, 1.34; 95% CI, 1.29 to 1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20 to 1.65; P < .001) and lower neck involvement (HR, 1.16; 95% CI, 1.06 to 1.27; P < .001) also predicted increased mortality. Increasing number of nodes examined was associated with improved survival, plateauing at 35 LNs (HR, 0.98; 95% CI, 0.98 to 0.99; P < .001). In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality. A novel nodal staging system derived by recursive partitioning analysis exhibited greater concordance than the American Joint Committee on Cancer (8th edition) system. Conclusion The number of metastatic nodes is a critical predictor of oral cavity cancer mortality, eclipsing other features such as LN size and contralaterality in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions.
Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of prostate SBRT. We therefore ...sought to systematically analyze biochemical recurrence-free survival (bRFS), physician-reported toxicity, and patient-reported outcomes after prostate SBRT.
A systematic search leveraging Medline via PubMed and EMBASE for original articles published between January 1990 and January 2018 was performed. This was supplemented by abstracts with sufficient extractable data from January 2013 to March 2018. All prospective series assessing curative-intent prostate SBRT for localized prostate cancer reporting bRFS, physician-reported toxicity, and patient-reported quality of life with a minimum of 1-year follow-up were included. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined by the I
and Cochran's Q tests. Meta-regression was performed using Hartung-Knapp methods.
Thirty-eight unique prospective series were identified comprising 6116 patients. Median follow-up was 39 months across all patients (range, 12-115 months). Ninety-two percent, 78%, and 38% of studies included low, intermediate, and high-risk patients. Overall, 5- and 7-year bRFS rates were 95.3% (95% confidence interval CI, 91.3%-97.5%) and 93.7% (95% CI, 91.4%-95.5%), respectively. Estimated late grade ≥3 genitourinary and gastrointestinal toxicity rates were 2.0% (95% CI, 1.4%-2.8%) and 1.1% (95% CI, 0.6%-2.0%), respectively. By 2 years post-SBRT, Expanded Prostate Cancer Index Composite urinary and bowel domain scores returned to baseline. Increasing dose of SBRT was associated with improved biochemical control (P = .018) but worse late grade ≥3 GU toxicity (P = .014).
Prostate SBRT has substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity demonstrated. SBRT has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority.
Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but ...are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life‐long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team.
Oral complications of radiation therapy to the head and neck can result in acute and long‐term deterioration in oral soft tissues and dentition. The presentation, prognosis, and strategies to manage the dental and nondental morbidities of radiation therapy to the head and neck are discussed in this manuscript.
Studies suggest that the efficacy of cancer chemotherapy and immunotherapy is influenced by intestinal bacteria. However, the influence of the microbiome on radiation therapy is not as well ...understood, and the microbiome comprises more than bacteria. Here, we find that intestinal fungi regulate antitumor immune responses following radiation in mouse models of breast cancer and melanoma and that fungi and bacteria have opposite influences on these responses. Antibiotic-mediated depletion or gnotobiotic exclusion of fungi enhances responsiveness to radiation, whereas antibiotic-mediated depletion of bacteria reduces responsiveness and is associated with overgrowth of commensal fungi. Further, elevated intratumoral expression of Dectin-1, a primary innate sensor of fungi, is negatively associated with survival in patients with breast cancer and is required for the effects of commensal fungi in mouse models of radiation therapy.
Display omitted
•Commensal bacteria support antitumor T cell responses following radiation therapy•Depletion of intestinal bacteria leads to expansion of commensal fungal populations•Commensal fungi promote pro-tumor macrophage actions by impeding antitumor T cells•Tumor-associated macrophages sense fungi through a Dectin-1-mediated mechanism
Depletion of commensal bacteria leads to expansion of commensal fungi and reduced antitumor immunity following irradiation of tumors. Targeting commensal fungi enhanced the radiation-induced antitumor immune response by reducing macrophage-mediated immunosuppression. Thus, Shiao et al. demonstrate opposing effects of commensal bacteria and fungi on antitumor immunity following radiation.
Abstract Background The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification. Objective We ...propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making. Design, setting, and participants Between 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥50%, or multiple intermediate-risk factors (IRFs; cT2b–c, prostate-specific antigen PSA 10–20, or Gleason score 7). Intervention All patients received EBRT with ≥81 Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT). Outcome measurements and statistical analysis Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method. Results and limitations Median follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio HR: 3.26; p < 0.0001), PPBC ≥50% (HR: 2.72; p = 0.0007), and multiple IRFs (HR: 2.20; p = 0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p < 0.0001) and PPBC ≥50% (HR: 4.08; p = 0.002) but not multiple IRFs (HR: 1.74; p = 0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p < 0.0001), DM (HR: 4.34; p = 0.0003), and PCSM (HR: 7.39; p = 0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations. Conclusions Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms.
Abstract Background In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC). ...Objective To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC. Design, setting, and participants Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States. Intervention Use of metformin in localized prostate cancer. Outcome measurements and statistical analysis Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality (PCSM), overall survival (OS), and development of CRPC. Results and limitations With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio HR: 1.99 1.24–3.18; p = 0.004), DMFS (adjusted HR: 3.68 1.78–7.62; p < 0.001), and PCSM (HR: 5.15 1.53–17.35; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 1.83–119.89; p = 0.01). The retrospective study design was the primary limitation of the study. Conclusions To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted.
PDF
