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BackgroundAge is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions.MethodsA total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model.ResultsUsing age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92.ConclusionsA change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

Purpose: To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer.Materials and Methods: This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant Ktrans on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC).Results: For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR.Conclusion: Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement.Key Points: • Volumetry on post-treatment DCE-/DW-MRI sequences correlated well with histopathological tumour regression. • DCE-MRI volumetry demonstrated good inter-reader agreement. • Inter-reader agreement was higher for DCE-MRI volumetry than for DW-MRI volumetry. • DCE-MRI volumetry merits further investigation as a metric for evaluating treatment response. [ABSTRACT FROM AUTHOR]

Background: Improvements in liver surgery have led to decreased mortality rates. Symptomatic perihepatic collections (SPHCs) requiring percutaneous drainage remain a significant source of morbidity.Study Design: A single institution's prospectively maintained hepatic resection database was reviewed to identify patients who underwent hepatectomy between January 2004 and February 2012.Results: Data from 2173 hepatectomies performed in 2040 patients were reviewed. Overall, 200 (9%) patients developed an SPHC, the majority non-bilious (75.5%) and infected (54%). Major hepatic resections, larger than median blood loss (≥360 ml), use of surgical drains, and simultaneous performance of a colorectal procedure were associated with an SPHC on multivariate analysis. Non-bilious, non-infected (NBNI) collections were associated with lower white blood cell (WBC) counts, absence of a bilio-enteric anastomosis, use of hepatic arterial infusion pump (HAIP), and presence of metastatic disease, and resolved more frequently with a single interventional radiology (IR) procedure (85 vs. 46.5%, p < 0.001) more quickly (15 vs. 30 days, p = 0.001).Conclusions: SPHCs developed in 9% of patients in a modern series of hepatic resections, and in one third were non-bilious and non-infected. In the era of modern interventional radiology, the need for re-operation for SPHC is exceedingly rare. A significant proportion of minimally symptomatic SPHC patients may not require drainage, and strategies to avoid unnecessary drainage are warranted. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the significance of pathologic nodal assessment and extent of nodal metastases on patient outcome in patients with pancreatic adenocarcinoma.Materials and Methods: A prospectively maintained pancreatic cancer database was reviewed, and 696 consecutive patients were identified who underwent resection for pancreatic adenocarcinoma between 1995 and 2005. Overall survival was compared to lymph node (LN) status, absolute number of pathologically assessed LN, and LN ratio expressed as the number of positive LN to the total LN assessed.Results: Of the 696 patients, 598 (86%) had pancreaticoduodenectomy (PD), and 96 (14%) had distal pancreatectomy (DP). For all patients, median follow-up was 13 months (range, 0-122 months), and estimated 5-year survival was 16%. A total of 243 (35%) patients were LN-negative (N0) and had a median survival of 27 months. When assessed as a continuous variable, the number of pathologically assessed LN did not correlate with survival for N0 patients undergoing either PD or DP. The median survival for the 453 patients with node-positive (N1) disease was 16 months. When analyzed as a continuous variable, the absolute number of positive LNs was a significant predictor of survival for N1 patients with a linear relationship up to eight positive LNs. LN ratio, as a continuous variable, also predicted survival with a linear relationship up to a ratio of 0.35. A ratio of 0.18 was associated with a 19-month median survival and served as the best cutoff, p < 0.01.Conclusions: The absolute number of positive LNs and LN ratio are strong predictors of survival for patients with node-positive pancreatic adenocarcinoma. Inadequate surgical lymphadenectomy or pathologic LN assessment understages node-negative patients. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone.Methods: Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing.Results: Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months).Conclusions: In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: To determine if the histology of a breast malignancy influences the appearance of untreated osseous metastases on FDG PET/CT. Methods: This retrospective study was performed under IRB waiver. Our Hospital Information System was screened for breast cancer patients who presented with osseous metastases, who underwent FDG PET/CT prior to systemic therapy or radiotherapy from 2009 to 2012. Patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or mixed ductal/lobular (MDL) histology were included. Patients with a history of other malignancies were excluded. PET/CT was evaluated, blinded to histology, to classify osseous metastases on a per-patient basis as sclerotic, lytic, mixed lytic/sclerotic, or occult on CT, and to record SUVmax for osseous metastases on PET. Results: Following screening, 95 patients who met the inclusion criteria (74 IDC, 13 ILC, and 8 MDL) were included. ILC osseous metastases were more commonly sclerotic and demonstrated lower SUVmax than IDC metastases. In all IDC and MDL patients with osseous metastases, at least one was FDG-avid. For ILC, all patients with lytic or mixed osseous metastases demonstrated at least one FDG-avid metastasis; however, in only three of seven patients were sclerotic osseous metastases apparent on FDG PET. Conclusion: The histologic subtype of breast cancer affects the appearance of untreated osseous metastases on FDG PET/CT. In particular, non-FDG-avid sclerotic osseous metastases were more common in patients with ILC than in patients with IDC. Breast cancer histology should be considered when interpreting non-FDG-avid sclerotic osseous lesions on PET/CT, which may be more suspicious for metastases (rather than benign lesions) in patients with ILC. [ABSTRACT FROM AUTHOR]

Purpose: Adverse symptom event reporting is vital as part of clinical trials and drug labeling to ensure patient safety and inform risk-benefit decision making. The purpose of this study was to assess the reliability of adverse event reporting of different clinicians for the same patient for the same visit. Methods: A retrospective reliability analysis was completed for a sample of 393 cancer patients (42.8% men; age 26-91, M = 62.39) from lung ( n = 134), prostate ( n = 113), and Ob/Gyn ( n = 146) clinics. These patients were each seen by two clinicians who independently rated seven Common Terminology Criteria for Adverse Events (CTCAE) symptoms. Twenty-three percent of patients were enrolled in therapeutic clinical trials. Results: The average time between rater evaluations was 68 min. Intraclass correlation coefficients were moderate for constipation (0.50), diarrhea (0.58), dyspnea (0.69), fatigue (0.50), nausea (0.52), neuropathy (0.71), and vomiting (0.46). These values demonstrated stability over follow-up visits. Two-point differences, which would likely affect treatment decisions, were most frequently seen among symptomatic patients for constipation (18%), vomiting (15%), and nausea (8%). Conclusion: Agreement between different clinicians when reporting adverse symptom events is moderate at best. Modification of approaches to adverse symptom reporting, such as patient self-reporting, should be considered. [ABSTRACT FROM AUTHOR]

Background: Liver angiomyolipomas (AML) are mesenchymal neoplasms with an uncertain clinical behavior. The spectrum of presentation, imaging and histologic features, and outcomes were analyzed in all patients treated at Memorial Sloan-Kettering Cancer Center. Methods: Demographics, disease, pathologic, treatment, and outcome-related variables for consecutive patients were reviewed retrospectively. All imaging studies obtained at presentation were reexamined, categorized, and compared using Fisher and Wilcoxon tests. Results: Between 1989 and 2010, 238 patients with AML were seen and 22 (9.3%) had liver involvement (exclusive = 17; combined with kidney = 5). The median age was 53 years; 18 were females, and 15 had symptoms. AML was not suspected at initial presentation in any patient. Fat-containing neoplasms on imaging were larger (P = .03), with more heterogeneous enhancement compared with fat-poor neoplasms (P = .001), but none of the imaging/histologic features correlated with outcome. Thirteen patients underwent resection (R0 = 9), 4 were observed, 2 received chemotherapy, 2 embolization, and 1 embolization plus intra-arterial chemotherapy. Two patients treated with R0-resection recurred and 2 treated with chemotherapy progressed, but no patient died of AML-related causes. At a median follow-up of 36 months, 7 patients were free of disease, 13 were alive with disease, 1 died of an unrelated cause, and another was lost to follow-up. Conclusion: AMLs are rare neoplasms with an indolent course in most patients. Subtypes based on fat content are recognized, but clinical behavior does not seem to be different. Recurrence after resection is not associated with disease-related mortality. Resection may be unnecessary in selected asymptomatic patients if the diagnosis can be established definitively. [ABSTRACT FROM AUTHOR]

Quantitative analysis of computed tomography (CT) scans of patients with metastatic colorectal cancer (mCRC) can identify imaging signatures that predict overall survival (OS). We retrospectively analysed CT images from 1584 mCRC patients on two phase III trials evaluating FOLFOX ± panitumumab (n = 331, 350) and FOLFIRI ± aflibercept (n = 437, 466). In the training set (n = 720), an algorithm was trained to predict OS landmarked from month 2; the output was a signature value on a scale from 0 to 1 (most to least favourable predicted OS). In the validation set (n = 864), hazard ratios (HRs) evaluated the association of the signature with OS using RECIST1.1 as a benchmark of comparison. In the training set, the selected signature combined three features – change in tumour volume, change in tumour spatial heterogeneity, and tumour volume – to predict OS. In the validation set, RECIST1.1 classified patients in three categories: response (n = 166, 19.2%), stable disease (n = 636, 73.6%), and progression (n = 62, 7.2%). The HR was 3.93 (2.79–5.54). Using the same distribution for the signature, the HR was 21.04 (14.88–30.58), showing an incremental prognostic separation. Stable disease by RECIST1.1 was reclassified by the signature along a continuum where patients belonging to the most and least favourable signature quartiles had a median OS of 40.73 (28.49 to NA) months (n = 94) and 7.03 (5.66–7.89) months (n = 166), respectively. A signature combining three imaging features provides early prognostic information that can improve treatment decisions for individual patients and clinical trial analyses. • Response evaluation using RECIST1.1 generalises across tissues and treatments. • Radiomics can better predict survival for metastatic colorectal cancer patients. • Clinical trial data proved generalizability across lesion sites and treatment arms. • This approach can evaluate patients at minimal cost using standard of care CT. [ABSTRACT FROM AUTHOR]

Anti-PD-(L)1 immunotherapies improve survival in multiple cancers but remain ineffective for most patients. We applied machine-learning algorithms and multivariate analyses on baseline medical data to estimate their relative impact on overall survival (OS) upon anti-PD-(L)1 monotherapies. This prognostic/predictive study retrospectively analysed 33 baseline routine medical variables derived from computed tomography (CT) images, clinical and biological meta-data. 695 patients with a diagnosis of advanced cancer were treated in prospective clinical trials in a single tertiary cancer centre in 3 cohorts including systemic anti-PD-(L)1 (251, 235 patients) versus other systemic therapies (209 patients). A random forest model combined variables to identify the combination (signature) which best estimated OS in patients treated with immunotherapy. The performance for estimating OS [95%CI] was measured using Kaplan–Meier Analysis and Log–Rank test. Elevated serum lactate dehydrogenase (LDHhi) and presence of liver metastases (LM+) were dominant and independent predictors of short OS in independent cohorts of melanoma and non-melanoma solid tumours. Overall, LDHhiLM+ patients treated with anti-PD-(L)1 monotherapy had a poorer outcome (median OS: 3.1[2.4–7.8] months]) compared to LDHlowLM-patients (median OS: 15.3[8.9-NA] months; P < 0.0001). The OS of LDHlowLM-patients treated with immunotherapy was 28.8[17.9-NA] months (vs 13.1[10.8–18.5], P = 0.02) in the overall population and 30.3[19.93-NA] months (vs 14.1[8.69-NA], P = 0.0013) in patients with melanoma. LDHhiLM+ status identifies patients who shall not benefit from anti-PD-(L)1 monotherapy. It could be used in clinical trials to stratify patients and eventually address this specific medical need. • A baseline machine learning-derived signature predicted survival on immunotherapy. • LDHhi (elevated serum LDH) and LM+ (liver metastasis) forecasted short survival. • LDHlow LM-forecasted longer survival with immunotherapy than other systemic therapies. • LDH LM status could guide clinical decision making for advanced cancer patients. [ABSTRACT FROM AUTHOR]

Background: This study analyzes factors associated with differences in long-term outcomes after hepatic resection for metastatic colorectal cancer over time. Study Design: Sixteen-hundred consecutive patients undergoing hepatic resection for metastatic colorectal cancer between 1985 and 2004 were analyzed retrospectively. Patients were grouped into 2 eras according to changes in availability of systemic chemotherapy: era I, 1985 to 1998; era II, 1999 to 2004. Results: There were 1,037 patients in era I and 563 in era II. Operative mortality decreased from 2.5% in era I to 1% in era II (p = 0.04). There were no differences in age, Clinical Risk Score, or number of hepatic metastases between the 2 groups; however, more recently treated patients (era II) had more lymph node–positive primary tumors, shorter disease-free intervals, more extrahepatic disease, and smaller tumors. Median follow-up was 36 months for all patients and 63 months for survivors. Median and 5-year disease-specific survival (DSS) were better in era II (64 months and 51% versus 43 months and 37%, respectively; p < 0.001); but median and 5-year recurrence-free survival (RFS) for all patients were not different (23 months and 33% era II versus 22 months and 27% era I; p = 0.16). There was no difference in RFS or DSS for high-risk (Clinical Risk Score >2, n = 506) patients in either era. There was a marked improvement in both RFS and DSS for low risk (Clinical Risk Score ≤2, n = 1,094) patients. Conclusions: Despite worse clinical and pathologic characteristics, survival but not recurrence rates after hepatic resection for colorectal metastases have improved over time and might be attributable to improvements in patient selection, operative management, and chemotherapy. The improvement in survival over time is largely accounted for by low-risk patients. [Copyright &y& Elsevier]

Purpose: Positron emission-tomography (PET) using 2-[(18)F]fluoro-2-deoxyglucose (FDG-PET) increases sensitivity and specificity of disease detection in lymphoma and thus is standard in lymphoma management. This study examines the effects of coregistering FDG-PET and computed tomography (CT) (PET/CT) scans on treatment planning for lymphoma patients. Methods and Materials: Twenty-nine patients (30 positive PET scans) underwent PET/CT treatment planning from July 2004 to February 2007 and were retrospectively studied. For each patient, gross tumor volume was blindly contoured on the CT-only and PET/CT studies by a radiation oncologist. Treatment plans were generated for both the CT-only and PET/CT planning target volumes (PTVs) for all patients. Normal tissue doses and PTV coverage were evaluated using dose--volume histograms for all sites. Results: Thirty-two treatment sites were evaluated. Twenty-one patients had non-Hodgkin lymphoma, 5 patients had Hodgkin lymphoma, and 3 patients had plasma cell neoplasms. Previously undetected FDG-avid sites were identified in 3 patients during PET/CT simulation, resulting in one additional treatment field. Due to unexpected PET/CT simulation findings, 2 patients did not proceed with radiation treatment. The addition of PET changed the volume of 23 sites (72%). The PTV was increased in 15 sites (47%) by a median of 11% (range, 6-40%) and reduced in 8 sites (25%) by a median of 20% (range, 6%-75%). In six (19%) replanned sites, the CT-based treatment plan would not have adequately covered the PTV defined by PET/CT. Conclusions: Incorporation of FDG-PET into CT-based treatment planning for lymphoma patients resulted in considerable changes in management, volume definition, and normal tissue dosimetry for a significant number of patients. [ABSTRACT FROM AUTHOR]