Faculty Bibliography

BACKGROUND:Accurate survival estimates are important for cancer control planning. Although observed survival estimates are unavailable for many countries, where they are available, wide variations are reported. Understanding the impact of specific treatment and imaging modalities can help decision makers to effectively allocate resources to improve cancer survival in their local context. METHODS:We developed a microsimulation model of stage-specific cancer survival in 200 countries and territories for 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) comprising 60% of global diagnosed cancer cases. The model accounts for country-specific availability of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy) and imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), as well as quality of care. We calibrated the model to reported survival estimates from CONCORD-3 (which reports global trends in cancer survival in 2000-14). We estimated 5-year net survival for diagnosed cancers in each country or territory and estimated potential survival gains from increasing the availability of individual treatment and imaging modalities, and more comprehensive packages of scale-up of these interventions. We report the mean and 95% uncertainty intervals (UIs) for all outcomes, calculated as the 2·5 and 97·5 percentiles of the simulation results. FINDINGS:The estimated global 5-year net survival for all 11 cancers combined is 42·6% (95% uncertainty interval 40·3-44·3), with survival in high-income countries being an average of 12 times (range 4-17) higher than that in low-income countries. Expanding availability of surgery or radiotherapy or improving quality of care would yield the largest survival gains in low-income (2·5-3·4 percentage point increase in survival) and lower-middle-income countries (2·4-6·1 percentage point increase), whereas upper-middle-income and high-income countries are more likely to benefit from improved availability of targeted therapy (0·7 percentage point increase for upper-middle income and 0·4 percentage point increase for high income). Investing in medical imaging will also be necessary to achieve substantial survival gains, with traditional modalities estimated to provide the largest gains in low-income settings, while MRI and PET would yield the largest gains in higher-income countries. Simultaneous expansion of treatment, imaging, and quality of care could improve 5-year net survival by more than ten times in low-income countries (3·8% [95% UI 0·5-9·2] to 45·2% [40·2-52·1]) and could more than double 5-year net survival in lower-middle-income countries (20·1% [7·2-31·7] to 47·1% [42·8-50·8]). INTERPRETATION:Scaling up both treatment and imaging availability could yield synergistic survival gains for patients with cancer. Expanding traditional modalities in lower-income settings might be a feasible pathway to improve survival before scaling up more modern technologies. FUNDING:Harvard T H Chan School of Public Health.

PURPOSE/OBJECTIVE:To assess the spectrum of computed tomography (CT) findings in patients with genitourinary cancers visiting the emergency room (ER) and evaluate the relationship between CT findings and overall survival (OS). METHODS:Retrospective analysis of consecutive patients with genitourinary cancers undergoing CT during an ER visit at a tertiary cancer center during a 20-month period. CTs were considered positive if there were findings relevant to the presenting complaint(s). Demographic/clinical variables were recorded. OS was evaluated using Kaplan-Meier curves. Univariate and multivariate Cox proportional hazards regression (HR) was used to evaluate OS predictors. RESULTS:Two hundred twenty-seven patients (243 visits) were included. The most common primary tumors were prostate (121 [49.8%]), bladder/urothelial (78 [32.1%]), and renal (69 [28.4%]). Common presenting complaints were abdominal pain (67 [27.6%]), respiratory symptoms (49 [20.2%]), neurological signs (37 [15.2%]), and fever (34 [14.0%]). CT findings were positive in 172 patients (70.8%) and included new/increased metastases (21.4% [52/243]), fluid collections (7.4% [18/243]), urinary tract infection/inflammation (6.2% [15/243]), enteritis/colitis (5.3% [13/243]), and pneumonia (4.9% [12/243]). A positive ER CT was associated with patient admission (p = 0.01). At multivariate analysis, independently predictive factors of shorter survival were positive ER CT (HR = 2.09 [95% CI 1.16-3.76, p = 0.01), hospital admission (HR = 2.17 [95% CI 1.38-3.41], p < 0.01), and recent systemic treatment (HR = 2.10 [95% CI 1.32-3.35], p < 0.01). CONCLUSION/CONCLUSIONS:When CT was performed, it was able to identify a structural cause for the presenting complaint in the majority of patients with genitourinary cancers attending the ER. A positive ER CT was associated with hospital admission and poorer overall survival.

OBJECTIVES/OBJECTIVE:To investigate the association between CT imaging traits and texture metrics with proteomic data in patients with high-grade serous ovarian cancer (HGSOC). METHODS:This retrospective, hypothesis-generating study included 20 patients with HGSOC prior to primary cytoreductive surgery. Two readers independently assessed the contrast-enhanced computed tomography (CT) images and extracted 33 imaging traits, with a third reader adjudicating in the event of a disagreement. In addition, all sites of suspected HGSOC were manually segmented texture features which were computed from each tumor site. Three texture features that represented intra- and inter-site tumor heterogeneity were used for analysis. An integrated analysis of transcriptomic and proteomic data identified proteins with conserved expression between primary tumor sites and metastasis. Correlations between protein abundance and various CT imaging traits and texture features were assessed using the Kendall tau rank correlation coefficient and the Mann-Whitney U test, whereas the area under the receiver operating characteristic curve (AUC) was reported as a metric of the strength and the direction of the association. P values < 0.05 were considered significant. RESULTS:Four proteins were associated with CT-based imaging traits, with the strongest correlation observed between the CRIP2 protein and disease in the mesentery (p < 0.001, AUC = 0.05). The abundance of three proteins was associated with texture features that represented intra-and inter-site tumor heterogeneity, with the strongest negative correlation between the CKB protein and cluster dissimilarity (p = 0.047, τ = 0.326). CONCLUSION/CONCLUSIONS:This study provides the first insights into the potential associations between standard-of-care CT imaging traits and texture measures of intra- and inter-site heterogeneity, and the abundance of several proteins. KEY POINTS/CONCLUSIONS:• CT-based texture features of intra- and inter-site tumor heterogeneity correlate with the abundance of several proteins in patients with HGSOC. • CT imaging traits correlate with protein abundance in patients with HGSOC.

PURPOSE:We studied the risk of metastatic prostate cancer development in men with Grade Group 2 disease managed with active surveillance at Memorial Sloan Kettering Cancer Center. MATERIALS AND METHODS:A total of 219 men with Grade Group 2 prostate cancer had disease managed with active surveillance between 2000 and 2017. Biopsy was performed every 2 to 3 years, or upon changes in magnetic resonance imaging, prostate specific antigen level or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival. RESULTS:Median age at diagnosis was 67 years (IQR 61-72), median prostate specific antigen was 5 ng/ml (IQR 4-7) and most patients (69%) had nonpalpable disease. During followup 64 men received treatment, including radical prostatectomy in 36 (56%), radiotherapy in 20 (31%), hormone therapy in 3 (5%) and focal therapy in 5 (8%). Of the 36 patients who underwent radical prostatectomy 32 (89%) had Grade Group 2 disease on pathology and 4 (11%) had Grade Group 3 disease. Treatment-free survival was 61% (95% CI 52-70) at 5 years and 49% (95% CI 37-60) at 10 years. Three men experienced biochemical recurrence, no men had distant metastasis and no men died of prostate cancer during the followup. Median followup was 3.1 years (IQR 1.9-4.9). CONCLUSIONS:Active surveillance appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer treated at a tertiary cancer center. Definitive conclusions await further followup.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.

PURPOSE:We report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance at a tertiary cancer center. MATERIALS AND METHODS:A total of 2,907 patients were managed with active surveillance between 2000 and 2017, of whom 2,664 had Grade Group 1 disease. Patients were recommended confirmatory biopsy to verify eligibility and were followed semiannually with prostate specific antigen, digital rectal examination and review of symptoms. Magnetic resonance imaging was increasingly used in recent years. Biopsy was repeated every 2 to 3 years or after a sustained prostate specific antigen increase or changes in magnetic resonance imaging/digital rectal examination. The Kaplan-Meier method was used to estimate probabilities of treatment, progression and development of metastasis. RESULTS:Median patient age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer the treatment-free probability at 5, 10 and 15 years was 76% (95% CI 74-78), 64% (95% CI 61-68) and 58% (95% CI 51-64), respectively. At 5, 10 and 15 years there were 1,146, 220 and 25 men at risk for metastasis, respectively. Median followup for those without metastasis was 4.3 years (95% CI 2.3-6.9). Distant metastasis developed in 5 men. Upon case note review only 2 of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2-2.0) at 10 years. CONCLUSIONS:Active surveillance is a safe strategy over longer followup for appropriately selected patients with Grade Group 1 disease following a well-defined monitoring plan.

The urachus is a fibrous tube extending from the umbilicus to the anterosuperior bladder dome that usually obliterates at week 12 of gestation, becoming the median umbilical ligament. Urachal pathology occurs when there is incomplete obliteration of this channel during foetal development, resulting in the formation of a urachal cyst, patent urachus, urachal sinus or urachal diverticulum. Patients with persistent urachal remnants may be asymptomatic or present with lower abdominal or urinary tract symptoms and can develop complications. The purpose of this review is to describe imaging features of urachal remnant pathology and potential benign and malignant complications on ultrasound, CT, positron emission tomography CT and MRI.

OBJECTIVE:The purpose was to review the diagnostic performance of the length of tumor capsular contact (LCC) on magnetic resonance imaging (MRI) for detecting prostate cancer extraprostatic extension (EPE). MATERIALS AND METHODS:PubMed and EMBASE databases were searched up to March 24, 2019. We included diagnostic accuracy studies that evaluated LCC on MRI for EPE detection using radical prostatectomy specimen histopathology as the reference standard. Quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity were pooled and graphically presented using hierarchical summary receiver operating characteristic (HSROC) plots. Meta-regression and subgroup analyses were conducted to explore heterogeneity. RESULTS:= 0.14-0.93). Diagnostic test accuracy estimates were comparable across all assessed MRI sequences. CONCLUSION:Greater LCC on MRI is associated with a higher probability of prostate cancer EPE. Due to heterogeneity among the studies, further investigation is needed to establish the optimal cutoff value for each clinical setting.