Cancer Screening Rates in Individuals With Different Life Expectancies

IMPORTANCE: Routine cancer screening has unproven net benefit for patients with limited life expectancy. OBJECTIVE: To examine the patterns of prostate, breast, cervical, and colorectal cancer screening in the United States in individuals with different life expectancies. DESIGN, SETTING, AND PARTICIPANTS: Data from the population-based National Health Interview Survey (NHIS) from 2000 through 2010 were used and included 27 404 participants aged 65 years or older. Using a validated mortality index specific for NHIS, participants were grouped into those with low (<25%), intermediate (25%-49%), high (50%-74%), and very high (≥75%) risks of 9-year mortality. MAIN OUTCOMES AND MEASURES: Rates of prostate, breast, cervical, and colorectal cancer screening. RESULTS: In participants with very high mortality risk, 31% to 55% received recent cancer screening, with prostate cancer screening being most common (55%). For women who had a hysterectomy for benign reasons, 34% to 56% had a Papanicolaou test within the past 3 years. On multivariate analysis, very high vs low mortality risk was associated with less screening for prostate (odds ratio [OR], 0.65 [95% CI, 0.50-0.85]), breast (OR, 0.43 [95% CI, 0.35-0.53]), and cervical (OR, 0.50 [95% CI, 0.36-0.70]) cancers. There was less screening for prostate and cervical cancers in more recent years compared with 2000, and there was no significant interaction between calendar year and mortality risk for any cancer screening (P > .05 for all cancers). Our sensitivity analysis showed that screening was also common in individuals with less than 5-year life expectancy. CONCLUSIONS AND RELEVANCE: A substantial proportion of the US population with limited life expectancy received prostate, breast, cervical, and colorectal cancer screening that is unlikely to provide net benefit. These results suggest that overscreening is common in both men and women, which not only increases health care expenditure but can lead to net patient harm

High Dose “HDR-Like” Prostate SBRT: PSA 10-Year Results From a Mature, Multi-Institutional Clinical Trial

Purpose/Objective(s)Although ample intermediate-term prostate stereotactic body radiotherapy (SBRT) outcomes have been reported, 10-year results remain relatively sparse.Materials/MethodsEighteen institutions enrolled 259 low- and intermediate-risk patients. Median follow-up is 5.5 years, with 66 patients followed ≥ 10 years. This SBRT regimen specifically emulated an existing HDR brachytherapy dose schedule and isodose morphology, prescribed to 38 Gy/4 fractions, delivered daily by robotic SBRT, mandating > 150% dose escalation in the peripheral zone. Androgen deprivation therapy was not allowed, and a hydrogel spacer was not available at that time.ResultsMedian pre-SBRT PSA 5.12 ng/mL decreased to 0.1 ng/mL by 3.5 years, with further decrease to a nadir of < 0.1 ng/mL by 7 years, maintained through 10 years. Ten-year freedom from biochemical recurrence measured 100% for low-risk, 84.3% for favorable intermediate risk (FIR), and 68.4% for unfavorable intermediate (UIR) cases. Multivariable analysis revealed that the UIR group bifurcated into two distinct prognostic subgroups. Those so classified by having Gleason score 4 + 3 and/or clinical stage T2 (versus T1b/T1c) had a significantly poorer 10 year freedom from biochemical recurrence rate, 54.8% if either or both factors were present, while UIR patients without these specific factors had a 94.4% 10-year freedom from biochemical recurrence rate. The cumulative incidence of grade 2 GU toxicity modestly increased over time – 16.3% at 5 years increased to 19.2% at 10 years-- while the incidence of grade 3+ GU and GI toxicity remained low and stable to 10 years - 2.6% and 0%, respectively. The grade 2 GI toxicity incidence also remained low and stable to 10 years – 4.1% with no further events after year 5.ConclusionThis HDR-like SBRT regimen prescribing 38 Gy/4 fractions but delivering much higher intraprostatic doses on a daily basis is safe and effective. This treatment achieves a median PSA nadir of <0.1 ng/mL and provides high long-term disease control rates without ADT except for a subgroup of unfavorable intermediate-risk patients

High Dose “HDR-Like” Prostate SBRT: PSA 10-Year Results From a Mature, Multi-Institutional Clinical Trial

Purpose/Objective(s)Although ample intermediate-term prostate stereotactic body radiotherapy (SBRT) outcomes have been reported, 10-year results remain relatively sparse.Materials/MethodsEighteen institutions enrolled 259 low- and intermediate-risk patients. Median follow-up is 5.5 years, with 66 patients followed ≥ 10 years. This SBRT regimen specifically emulated an existing HDR brachytherapy dose schedule and isodose morphology, prescribed to 38 Gy/4 fractions, delivered daily by robotic SBRT, mandating &gt; 150% dose escalation in the peripheral zone. Androgen deprivation therapy was not allowed, and a hydrogel spacer was not available at that time.ResultsMedian pre-SBRT PSA 5.12 ng/mL decreased to 0.1 ng/mL by 3.5 years, with further decrease to a nadir of &lt; 0.1 ng/mL by 7 years, maintained through 10 years. Ten-year freedom from biochemical recurrence measured 100% for low-risk, 84.3% for favorable intermediate risk (FIR), and 68.4% for unfavorable intermediate (UIR) cases. Multivariable analysis revealed that the UIR group bifurcated into two distinct prognostic subgroups. Those so classified by having Gleason score 4 + 3 and/or clinical stage T2 (versus T1b/T1c) had a significantly poorer 10 year freedom from biochemical recurrence rate, 54.8% if either or both factors were present, while UIR patients without these specific factors had a 94.4% 10-year freedom from biochemical recurrence rate. The cumulative incidence of grade 2 GU toxicity modestly increased over time – 16.3% at 5 years increased to 19.2% at 10 years-- while the incidence of grade 3+ GU and GI toxicity remained low and stable to 10 years - 2.6% and 0%, respectively. The grade 2 GI toxicity incidence also remained low and stable to 10 years – 4.1% with no further events after year 5.ConclusionThis HDR-like SBRT regimen prescribing 38 Gy/4 fractions but delivering much higher intraprostatic doses on a daily basis is safe and effective. This treatment achieves a median PSA nadir of &lt;0.1 ng/mL and provides high long-term disease control rates without ADT except for a subgroup of unfavorable intermediate-risk patients

Sex Disparity and Copy Number Alterations in Esophageal Squamous Cell Carcinoma

Although sex differences in the incidence of esophageal cancer are well-established, the independent prognostic value of sex remains unclear. Recently, several groups have performed comprehensive molecular analyses of esophageal tumors,1 providing the opportunity to elucidate the underlying genomic bases for epidemiologic observations. We therefore sought to evaluate the effect of sex on esophageal cancer prognosis and to compare genomic data from tumors in men versus women

HPV status predicts for improved survival following chemotherapy in metastatic squamous cell carcinoma of the oropharynx

We sought to further define prognostic and predictive value of human papillomavirus (HPV) status in metastatic squamous cell carcinoma of the oropharynx (OPC). A Surveillance, Epidemiology, and End Results custom database identified 5940 adult patients, >18-years-old, with primary SCCHN and known HPV status, diagnosed from 2013 to 2014. Wilcoxon rank-sum and Mantel-Haenszel χ tests compared distributions of continuous and categorical covariates. Fine-Gray competing risks regressions estimated hazard ratios by HPV status, and predictive analyses were performed including the interaction term HPV status × Receipt of Chemotherapy. 182 of 5940 patients (4.0%) had metastatic OPC at diagnosis (106/3925 [2.7%] HPV+ and 76/1894 [4.0%] HPV-). HPV+ disease was prognostic for improved 20-month cancer-specific mortality (CSM) (47.1% vs 72.5%, HR 0.43, 95% CI 0.26-0.74, p = 0.002) on univariable analysis. HPV status was predictive of response to chemotherapy-adjusted HRs for receipt of chemotherapy were 0.11 (95% CI 0.03-0.37) and 0.34 (95% CI 0.18-0.64) for HPV+ versus HPV- disease, respectively (P  = 0.036). HPV status has known prognostic value in locally advanced OPC, but data on metastatic OPC are sparse. In this work, we demonstrate that HPV status is strongly prognostic for CSM in metastatic OPC and show for the first time that HPV status predicts for response to chemotherapy

Safety of combining radiotherapy with immune-checkpoint inhibition

Immune-checkpoint inhibitors targeting cytotoxic T- lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) have transformed the care of patients with a wide range of advanced-stage malignancies. More than half of these patients will also have an indication for treatment with radiotherapy. The effects of both radiotherapy and immune-checkpoint inhibition (ICI) involve a complex interplay with the innate and adaptive immune systems, and accumulating evidence suggests that, under certain circumstances, the effects of radiotherapy synergize with those of ICI to augment the antitumour responses typically observed with either modality alone and thus improve clinical outcomes. However, the mechanisms by which radiotherapy and immune-checkpoint inhibitors synergistically modulate the immune response might also affect both the type and severity of treatment-related toxicities. Moreover, in patients receiving immune-checkpoint inhibitors, the development of immune-related adverse events has been linked with superior treatment responses and patient survival durations, suggesting a relationship between the antitumour and adverse autoimmune effects of these agents. In this Review, we discuss the emerging data on toxicity profiles related to immune-checkpoint inhibitors and radiotherapy, both separately and in combination, their potential mechanisms, and the approaches to managing these toxicities

Trimodality therapy for HPV-positive oropharyngeal cancer: A population-based study: Trimodality therapy for HPV+ OPC

Although HPV status is a well-established prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), approximately 20% of HPV-positive patients die from their disease. We therefore sought to ascertain whether there is a benefit to trimodality therapy with surgery among patients with locally advanced (LA) disease receiving chemoradiation. The SEER Head and Neck with HPV Status Database identified adult patients with non-metastatic OPSCC between 2013 and 2014 with known HPV status who received chemoradiation as part of definitive treatment. The primary outcome was cancer-specific mortality (CSM) for locally-advanced (LA) (T3-T4, or N2-N3, per AJCC 7) versus early-stage (ES) (T1-T2 and N0-N1) disease, stratified by HPV status. The secondary outcome was overall survival (OS). Among 2974 patients who met study criteria, 671 patients (22.6%) received upfront surgery (trimodality therapy). In the LA setting, there was a significant reduction in CSM with trimodality therapy compared to chemoradiation alone in HPV-positive (Adjusted Hazard Ratio [AHR] 0.19, 95% Confidence Interval [CI] 0.04-0.80; P = 0.024), but not HPV-negative disease [P  = 0.04]. There was no benefit to trimodality therapy for ES disease, regardless of HPV status. There was also an improvement in OS with trimodality therapy for HPV-positive LA patients (AHR = 0.28, p = 0.006, 95% CI = 0.11-0.70). In contrast, trimodality therapy was not associated with improved OS for HPV-negative patients regardless of stage. HPV status may predict for improved outcomes with surgery/trimodality therapy in LA OPSCC. Our findings support prospective investigations to optimize care for the subset of HPV-positive patients who are at greatest risk of cancer death, where trimodality therapy may be appropriate