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.

BACKGROUND:Cervical cancer is the fourth most common cancer among women worldwide, causing more than 300 000 deaths globally each year. In addition to screening and prevention, effective cancer treatment is needed to reduce cervical cancer mortality. We discuss the role of imaging in cervical cancer management and estimate the potential survival effect of scaling up imaging in several different contexts. METHODS:Using a previously developed microsimulation model of global cancer survival, we estimated stage-specific cervical cancer 5-year net survival in 200 countries and territories. We evaluated the potential survival effect of scaling up treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), and imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single photon emission CT [SPECT]) to the mean level of high-income countries, both individually and in combination. FINDINGS:We estimate global cervical cancer 5-year net survival as 42·1% (95% uncertainty interval [UI] 33·8-48·5). Among individual imaging modalities, expanding MRI would yield the largest 5-year survival gains globally (data are absolute percentage point increase in survival 0·6, 95% UI 0·1-2·1), scaling up ultrasound would yield the largest gains in low-income countries (0·5, 0·0-3·7), expanding CT and x-ray would have the greatest effect in Latin America (0·8, 0·0-3·4) and Oceania (0·4, 0·0-3·2), and expanding PET would yield the largest gains in high-income countries (0·2, 0·0-0·8). Scaling up SPECT did not show major changes in any region. Among individual treatment modalities, scaling up radiotherapy would yield the largest absolute percentage point gains in low-income countries (5·2, 0·3-13·5), and expanding surgery would have the largest effect in lower-middle-income countries (7·4, 0·3-21·1) and upper-middle-income countries (0·8, 0·0-2·9). Estimated survival gains in high-income countries were very modest. However, the gains from expanding any single treatment or imaging modality individually were small across all income levels and geographical settings. Scaling up all treatment modalities could improve global 5-year net survival to 52·4% (95% UI 44·6-62·0). In addition to expanding treatment, improving quality of care could raise survival to 57·5% (51·2-63·5), and the cumulative effect of scaling up all imaging modalities together with expanded treatment and quality of care could improve 5-year net survival for cervical cancer to 62·5% (57·7-67·8). INTERPRETATION:Comprehensive scale-up of treatment, imaging, and quality of care could substantially improve global cervical cancer 5-year net survival, with quality of care and imaging improvements each contributing about 25% of the total potential gains. These findings suggest that a narrow focus on the availability of treatment modalities could forgo substantial survival gains. Investments in imaging equipment, personnel, and quality of care efforts will also be needed to successfully scale up cervical cancer treatment worldwide. FUNDING:Harvard T H Chan School of Public Health and National Cancer Institute.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

Purpose: Develop an integrated intra-site and inter-site radiomics-clinical-genomic marker of high grade serous ovarian cancer (HGSOC) outcomes and explore the biological basis of radiomics with respect to molecular signaling pathways and the tumor microenvironment (TME). Method: Seventy-five stage III-IV HGSOC patients from internal (N = 40) and external factors via the Cancer Imaging Archive (TCGA) (N = 35) with pre-operative contrast enhanced CT, attempted primary cytoreduction, at least two disease sites, and molecular analysis performed within TCGA were retrospectively analyzed. An intra-site and inter-site radiomics (cluDiss) measure was combined with clinical-genomic variables (iRCG) and compared against conventional (volume and number of sites) and average radiomics (N = 75) for prognosticating progression-free survival (PFS) and platinum resistance. Correlation with molecular signaling and TME derived using a single sample gene set enrichment that was measured. Results: The iRCG model had the best platinum resistance classification accuracy (AUROC of 0.78 [95% CI 0.77 to 0.80]). CluDiss was associated with PFS (HR 1.03 [95% CI: 1.01 to 1.05], p = 0.002), negatively correlated with Wnt signaling, and positively to immune TME. Conclusions: CluDiss and the iRCG prognosticated HGSOC outcomes better than conventional and average radiomic measures and could better stratify patient outcomes if validated on larger multi-center trials.

To date, there is little consensus on the role of pelvic imaging in assessing local disease extent during initial staging in patients with endometrial carcinoma, with practices differing widely across centers. However, when pretreatment assessment of local tumor extent is indicated, MRI is the preferred imaging modality. Preoperative imaging of endometrial carcinoma can define the extent of disease and indicate the need for subspecialist referral in the presence of deep myometrial invasion, cervical extension, or suspected lymphadenopathy. If distant metastatic disease is clinically suspected, preoperative assessment with cross-sectional imaging or PET/CT may be performed. However, most patients with low-grade disease are at low risk of lymph node and distant metastases. Thus, this group may not require a routine pretreatment evaluation for distant metastases. Recurrence rates in patients with endometrial carcinoma are infrequent. Therefore, radiologic evaluation is typically used only to investigate suspicion of recurrent disease due to symptoms or physical examination and not for routine surveillance after treatment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Purpose/UNASSIGNED:To investigate the feasibility of accelerating prostate diffusion-weighted imaging (DWI) by reducing the number of acquired averages and denoising the resulting image using a proposed guided denoising convolutional neural network (DnCNN). Materials and Methods/UNASSIGNED:-value DW image as a guidance input. Quantitative and qualitative reader evaluations were performed on the denoised hb DW images. A cumulative link mixed regression model was used to compare the readers' scores. The agreement between the apparent diffusion coefficient (ADC) maps (denoised vs reference) was analyzed using Bland-Altman analysis. Results/UNASSIGNED:/sec). Conclusion/UNASSIGNED:© RSNA, 2020.

PURPOSE/OBJECTIVE:F-FDG PET/CT for detecting nodal metastases in patients with muscle-invasive urothelial bladder cancer prior to radical cystectomy. MATERIALS AND METHODS/METHODS:F-FDG PET/CT was assessed according to sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS:F-FDG PET/CT was useful in ruling out lymph node metastases (sensitivity 92-100%). This study was limited by its mixed population and focus on pelvic nodal metastases only. CONCLUSIONS:F-FDG PET/CT has limited utility in clinically node-negative patients.

PURPOSE/OBJECTIVE:Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS:An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS:A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS/CONCLUSIONS:One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.