Magnetic resonance imaging in naso-oropharyngeal carcinoma: role of texture analysis in the assessment of response to radiochemotherapy, a preliminary study.

OBJECTIVE: Identifying MRI texture parameters able to distinguish inflammation, fibrosis, and residual cancer in patients with naso-oropharynx carcinoma after radiochemotherapy (RT-CHT). MATERIAL AND METHODS: In this single-centre, observational, retrospective study, texture analysis was performed on ADC maps and post-gadolinium T1 images of patients with histological diagnosis of naso-oropharyngeal carcinoma treated with RT-CHT. An initial cohort of 99 patients was selected; 57 of them were later excluded. The final cohort of 42 patients was divided into 3 groups (inflammation, fibrosis, and residual cancer) according to MRI, 18F-FDG-PET/CT performed 3-4 months after RT-CHT, and biopsy. Pre-RT-CHT lesions and the corresponding anatomic area post-RT-CHT were segmented with 3D slicer software from which 107 textural features were derived. T-Student and Wilcoxon signed-rank tests were performed, and features with p-value < 0.01 were considered statistically significant. Cut-off values-obtained by ROC curves-to discriminate post-RT-CHT non-tumoural changes from residual cancer were calculated for the parameters statistically associated to the diseased status at follow-up. RESULTS: Two features-Energy and Grey Level Non-Uniformity-were statistically significant on T1 images in the comparison between 'positive' (residual cancer) and 'negative' patients (inflammation and fibrosis). Energy was also found to be statistically significant in both patients with fibrosis and residual cancer. Grey Level Non-Uniformity was significant in the differentiation between residual cancer and inflammation. Five features were statistically significant on ADC maps in the differentiation between 'positive' and 'negative' patients. The reduction in values of such features between pre- and post-RT-CHT was correlated with a good response to therapy. CONCLUSIONS: Texture analysis on post-gadolinium T1 images and ADC maps can differentiate residual cancer from fibrosis and inflammation in early follow-up of naso-oropharyngeal carcinoma treated with RT-CHT.

Association of Deficits Identified by Geriatric Assessment With Deterioration of Health-Related Quality of Life in Patients Treated for Head and Neck Cancer.

Importance: Accumulation of geriatric deficits, leading to an increased frailty state, makes patients susceptible for decline in health-related quality of life (HRQOL) after treatment for head and neck cancer (HNC). Objective: To assess the association of single and accumulated geriatric deficits with HRQOL decline in patients after treatment for HNC. Design, Setting, and Participants: Between October 2014 and May 2016, patients at a tertiary referral center were included in the Oncological Life Study (OncoLifeS), a prospective data biobank, and followed up for 2 years. A consecutive series of 369 patients with HNC underwent geriatric assessment at baseline; a cohort of 283 patients remained eligible for analysis, and after 2 years, 189 patients remained in the study. Analysis was performed between March and November 2020. Interventions or Exposures: Geriatric assessment included scoring of the Adult Comorbidity Evaluation 27, polypharmacy, Malnutrition Universal Screening Tool, Activities of Daily Living, Instrumental Activities of Daily Living (IADL), Timed Up & Go, Mini-Mental State Examination, 15-item Geriatric Depression Scale, marital status, and living situation. Main Outcomes and Measures: The primary outcome measure was the Global Health Status/Quality of Life (GHS/QOL) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Differences between patients were evaluated using linear mixed models at 3 months after treatment (main effects, ß [95% CI]) and declining course per year during follow-up (interaction × time, ß [95% CI]), adjusted for baseline GHS/QOL scores, and age, sex, stage, and treatment modality. Results: Among the 283 patients eligible for analysis, the mean (SD) age was 68.3 (10.9) years, and 193 (68.2%) were male. Severe comorbidity (ß = -7.00 [-12.43 to 1.56]), risk of malnutrition (ß = -6.18 [-11.55 to -0.81]), and IADL restrictions (ß = -10.48 [-16.39 to -4.57]) were associated with increased GHS/QOL decline at 3 months after treatment. Severe comorbidity (ß = -4.90 [-9.70 to -0.10]), IADL restrictions (ß = -5.36 [-10.50 to -0.22]), restricted mobility (ß = -6.78 [-12.81 to -0.75]), signs of depression (ß = -7.08 [-13.10 to -1.06]), and living with assistance or in a nursing home (ß = -8.74 [-15.75 to -1.73]) were associated with further GHS/QOL decline during follow-up. Accumulation of domains with geriatric deficits was a major significant factor for GHS/QOL decline at 3 months after treatment (per deficient domain ß = -3.17 [-5.04 to -1.30]) and deterioration during follow-up (per domain per year ß = -2.74 [-4.28 to -1.20]). Conclusions and Relevance: In this prospective cohort study, geriatric deficits were significantly associated with HRQOL decline after treatment for HNC. Therefore, geriatric assessment may aid decision-making, indicate interventions, and reduce loss of HRQOL. Trial Registration: trialregister.nl Identifier: NL7839.

Assessment of retroperitoneal lymph node status in locally advanced cervical cancer.

BACKGROUND: The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. METHODS: Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. RESULTS: The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD < 1.0 cm group (26.82%). The critical values of MAD and SCC-Ag in determining lymph node metastasis were 1.0 cm and 5.2 ng/mL, respectively. The accuracy, specificity, and Youden index of MAD ≥1.0 cm combined with SCC-Ag ≥ 5.2 ng/mL for evaluating lymph node metastasis were 75.71%, 100%, and 0.59, respectively, and were significantly different from the values for the MAD ≥1.0 cm (72.09%, 80.56%, and 0.47, respectively) and SCC-Ag ≥ 5.2 ng/mL (71.43%, 68.97%, and 0.42, respectively) groups. Correlation analysis showed that non-squamous cell carcinoma, pelvic lymph node (PLN) MAD ≥1.0 cm plus number ≥ 2, and 1 PLN MAD ≥1.0 cm with CILN and/or PALN MAD 0.5-1.0 cm were risk factors for CILN and/or PALN metastasis. CONCLUSION: Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD < 1.0 cm and SCC-Ag < 5.2 ng/mL may be treated with chemoradiotherapy directly based on imaging, given the low lymph node metastasis rate.

Impact of HER2 assessment by CISH in urothelial carcinoma: A retrospective single-center experience.

BACKGROUND: In recent years, HER2 amplification has been evaluated as a potential prognostic biomarker and therapeutic target in urothelial carcinoma (UC). In this retrospective study, we aimed at exploring the prognostic role of HER2 amplification in UC, measured by chromogenic in situ hybridization (CISH). METHODS: We retrospectively evaluated the presence of HER2 amplification by using CISH in 31 UC patients followed at a single institution between 2018 and 2020. The primary objective was to assess the frequency of HER2 amplification and to compare clinical outcomes of HER2-amplified patients with non-amplified UCs. RESULTS: HER2 amplification was identified in 4 out of 31 patients (12.9 %). After a median follow-up of 28.1 months (95 % Confidence Intervals [CI] 11.2-45.1), median overall survival (OS) in the whole population was 10.9 months (95 % CI 3.5-22.1). Despite not reaching statistical significance, median OS was shorter in HER2-amplified patients (6.8 months, 95 % CI 3.9-9.7) compared to HER2-negative UCs (15.4 months, 95 % CI 7.5-23.3) (p = 0.45). CONCLUSIONS: Although limited by the small sample size, the results of our study suggest that HER2 amplifications by CISH could represent a prognostic factor for shorter survival in UC patients.

Medical oncology referral and systemic therapy of patients with advanced stage urothelial carcinoma.

Aim: To understand physician visit patterns among patients with stage IV (including nonmetastatic [M0] and metastatic [M1] disease) urothelial carcinoma (UC) and understand factors associated with a timely referral to a medical oncologist and systemic treatment. Patients & methods: Retrospective analysis of Surveillance, Epidemiology and End Results-Medicare data. Results: First physician encounter was with a urologist (M0: 69%; M1: 53%) or primary care physician ([PCP]; M0: 19%, M1: 25%) for the majority of patients around UC diagnosis. After the index urologist encounter, most patients had a subsequent medical oncologist visit at a median of 52 days (M0: 69.5 days, M1: 33 days). In an adjusted model, older age, index PCP visit, higher comorbidities and M0 disease were negatively associated with a medical oncologist referral. Among those referred to a medical oncologist, older age, Hispanic or non-Hispanic Black race and not being married were negatively associated with subsequent chemotherapy receipt (p < 0.05). Conclusion: Many patients with advanced UC encounter multiple specialists during their disease course. Older patients or those with a first UC-related encounter with a PCP are less likely to be referred to medical oncology. Once referred to medical oncology, social determinants, including race and marital status, are relevant predictors of receiving chemotherapy.

Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. STUDY DESIGN: In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. RESULTS: Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. CONCLUSIONS: The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. (clinicaltrials.gov NCT325649).

First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma.

PURPOSE: Incomplete oncologic resections and damage to vital structures during colorectal cancer surgery increases morbidity and mortality. Moreover, neoadjuvant chemoradiotherapy has become the standard treatment modality for locally advanced rectal cancer, where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors and vital structures during surgery. EXPERIMENTAL DESIGN: We present the first-in-human clinical experience of a novel NIR fluorescent peptide, cRGD-ZW800-1, for the detection of colon cancer. cRGD-ZW800-1 was engineered to have an overall zwitterionic chemical structure and neutral charge to lower nonspecific uptake and thus background fluorescent signal. We performed a phase I study in 11 healthy volunteer as well as a phase II feasibility study in 12 patients undergoing an elective colon resection, assessing 0.005, 0.015, and 0.05 mg/kg cRGD-ZW800-1 for the intraoperative visualization of colon cancer. RESULTS: cRGD-ZW800-1 appears safe, and exhibited rapid elimination into urine after a single low intravenous dose. Minimal invasive intraoperative visualization of colon cancer through full-thickness bowel wall was possible after an intravenous bolus injection of 0.05 mg/kg at least 2 hours prior to surgery. Longer intervals between injection and imaging improved the tumor-to-background ratio. CONCLUSIONS: cRGD-ZW800-1 enabled fluorescence imaging of colon cancer in both open and minimal invasive surgeries. Further development of cRGD-ZW800-1 for widespread use in cancer surgery may be warranted given the ubiquitous overexpression of various integrins on different types of tumors and their vasculature.

Parietal cell/oncocytic gastric carcinoma: systematic review and first-time assessment of HER2 status in two new cases.

INTRODUCTION: Parietal cell/oncocytic gastric carcinomas are very rare and various aspects of this group remain unclear. The human epithelial growth factor receptor 2 (HER2) status of these tumours is largely unknown. METHODS: We performed a systematic electronic search of the literature and clinicopathological presentation of two cases including first-time complete assessment of HER2 status. Thirty-two patients with a mean age of 64.3 years, 87.5% of whom were male, were included in this review. FINDINGS: Half of the cases were recorded in Asia. Median follow-up was 24 months. There was no predominant site of development, while underlying histological abnormalities were present in 25%. At initial presentation, lymph node involvement was evident in 46.6% while distant metastatic disease was present in 9.3%. Presentation at stage I occurred in 55.6%. Potentially curative surgical/interventional treatment was intended in 90.6%. Recurrence occurred in 6.6%, while death was recorded in 19.2%, with cancer-related deaths reaching 11.5%. The one- and three-year survival rates were 84.2% and 79%, respectively. Our two cases displayed negative HER2 expression. CONCLUSIONS: This systematic review demonstrates that this group of malignancies is very rare but possibly underdiagnosed. The disease commonly presents at early stage, mainly affecting middle-aged men. The prognosis is generally favourable even in cases of advanced disease. The HER2 expression and its correlation with the outcomes need to be further explored.

Magnetic Resonance Assessment of Peritoneal Carcinomatosis: Is There a True Benefit From Diffusion-Weighted Imaging?

PURPOSE: To assess the added value of diffusion weighted imaging (DWI) with intermediate (500 s/mm2) and high (1000 s/mm2) b values when combined to conventional contrast-enhanced magnetic resonance imaging (MRI) in identifying peritoneal neoplastic involvement. METHODS: Twenty-four patients with peritoneal carcinomatosis from gastrointestinal or gynecological tumors were retrospectively evaluated. All patients underwent peritonectomy with hyperthermic intraoperative chemotherapy and 1.5 T MRI including DWI with 500 s/mm2 and 1000 s/mm2 b values within 1 month from surgery. Images were independently reviewed by 2 radiologists with different experience in abdominal MRI in 3 separate reading sessions, the first including conventional MR images alone (T2-weighted, T1-weighted pre- and post gadolinium injection), the second conventional MRI and DWI with a b value of 500 s/mm2 (b 500-DWI), and the third conventional MRI and DWI with a b value of 1000 s/mm2 (b 1000-DWI). Apparent diffusion coefficient maps were included in the DWI analyses. Peritoneal dissemination was assessed in 9 anatomical sites, including right and left subphrenic space, paracolic gutters, small bowel mesentery, greater omentum, gastric-bowel serosa, free peritoneal surfaces, rectosigmoid-colon mesentery, and pelvis. The presence or absence of peritoneal dissemination for each patient and for each site was scored using a 5-point confidence scale. Sensitivity, specificity, and area under the curve (AUC) for identifying per-site peritoneal implants were calculated for each reader at each reading session. Interobserver agreement was evaluated using kappa statistics. RESULTS: For both readers, the sensitivity and AUC values resulting from combined interpretation of conventional MRI and DWI (both b500-DWI and b1000-DWI) were significantly higher than those of conventional MRI alone (P < 0.001). The added value of DWI was greater for the less experienced reader (sensitivity 0.55, specificity 0.73, AUC 0.64 on conventional MRI; sensitivity 0.75, specificity 0.72, AUC 0.74 on b500-DWI; sensitivity 0.87, specificity 0.72, AUC 0.80 on b1000-DWI) than for the more experienced reader (sensitivity 0.63, specificity 0.75, AUC 0.70 on conventional MRI; sensitivity 0.76, specificity 0.77, AUC 0.77 on b500-DWI; sensitivity 0.85, specificity 0.72, AUC 0.79 on b1000-DWI), although the differences between the 2 observers were not statistically significant. Interobserver agreement resulted to be fair (κ = 0.30) when dealing with conventional MRI alone. The addition of b500-DWI and b1000-DWI to conventional MRI allowed to reach a substantial agreement (κ = 0.75). CONCLUSIONS: The combined interpretation of high b value DWI and conventional MRI provides increased sensitivity and diagnostic performance in detection of peritoneal carcinomatosis in oncologic patients.

Terminology, Molecular Features, Epidemiology, and Management of Serrated Colorectal Neoplasia.

In addition to the adenoma to carcinoma sequence, colorectal carcinogenesis can occur via the serrated pathway. Studies have focused on clarification of categories and molecular features of serrated polyps, as well as endoscopic detection and risk assessment. Guidelines from the World Health Organization propose assigning serrated polyps to categories of hyperplastic polyps, traditional serrated adenomas, and sessile serrated lesions (SSLs). Traditional serrated adenomas and SSLs are precursors to colorectal cancer. The serrated pathway is characterized by mutations in RAS and RAF, disruptions to the Wnt signaling pathway, and widespread methylation of CpG islands. Epidemiology studies of serrated polyps have been hampered by inconsistencies in terminology and reporting, but the prevalence of serrated class polyps is 20%-40% in average-risk individuals; most serrated polyps detected are hyperplastic. SSLs, the most common premalignant serrated subtype, and are found in up to 15% of average-risk patients by high-detecting endoscopists. Variations in rate of endoscopic detection of serrated polyps indicate the need for careful examination, with adequate bowel preparation and sufficient withdrawal times. Risk factors for SSLs include white race, family history of colorectal cancer, smoking, and alcohol intake. Patients with serrated polyps, particularly SSLs and traditional serrated adenomas, have an increased risk of synchronous and metachronous advanced neoplasia. Surveillance guidelines vary among countries, but SSLs and proximal hyperplastic polyps require special attention in assignment of surveillance interval-especially in light of concerns regarding incomplete detection and resection.

Assessment of 213Bi-anti-EGFR MAb treatment efficacy in malignant cancer cells with [1-13C]pyruvate and [18F]FDG.

Evaluation of response to therapy is among the key objectives of oncology. A new method to evaluate this response includes magnetic resonance spectroscopy (MRS) with hyperpolarized 13C-labelled metabolites, which holds promise to provide new insights in terms of both therapeutic efficacy and tumor cell metabolism. Human EJ28Luc urothelial carcinoma and LN18 glioma cells were treated with lethal activity concentrations of a 213Bi-anti-EGFR immunoconjugate. Treatment efficacy was controlled via analysis of DNA double-strand breaks (immunofluorescence γH2AX staining) and clonogenic survival of cells. To investigate changes in metabolism of treated cells vs controls we analyzed conversion of hyperpolarized [1-13C]pyruvate to [1-13C]lactate via MRS as well as viability of cells, lactate formation and lactate dehydrogenase activity in the cellular supernatants and [18F]FDG uptake in treated cells vs controls, respectively. Treatment of malignant cancer cells with 213Bi-anti-EGFR-MAb induced intense DNA double-strand breaks, resulting in cell death as monitored via clonogenic survival. Moreover, treatment of EJ28Luc bladder cancer cells resulted in decreased cell viability, [18F]FDG-uptake and an increased lactate export. In both EJ28Luc and LN18 carcinoma cells treatment with 213Bi-anti-EGFR-MAb triggered a significant increase in lactate/pyruvate ratios, as measured with hyperpolarized [1-13C]pyruvate. Treatment with 213Bi-anti-EGFR-MAb resulted in an effective induction of cell death in EJ28Luc and LN18 cells. Lactate/pyruvate ratios of hyperpolarized [1-13C]pyruvate proved to detect early treatment response effects, holding promise for future clinical applications in early therapy monitoring.

Prophylactic antibiotics reduce hospitalisations and cost in locally advanced head and neck cancer patients treated with chemoradiotherapy: A randomised phase 2 study.

BACKGROUND: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective. PATIENT AND METHODS: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis. The primary objective was to observe a reduction in pneumonias. Secondary objectives were to evaluate the hospitalisation rate, adverse events, costs and health-related quality of life. RESULTS: One hundred six patients were included; of which, 95 were randomised: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. A pneumonia during chemoradiotherapy and follow-up until 3.5 months was observed in 22 (45.8%) of 48 patients in the standard group and in 22 (46.8%) of 47 patients in the prophylaxis group (p = 0.54). Hospitalisation rate was significantly higher in the standard group versus the prophylaxis group, 19 of 48 pts (39.6%) versus 9 of 47 pts (19.1%), respectively (p = 0.03). Significantly more episodes with fever of any grade were observed in the standard group (29.2% vs 10.2%, p = 0.028). A significant difference in costs was found, with an average reduction of €1425 per patient in favour of the prophylaxis group. CONCLUSION: Although prophylactic antibiotics during chemoradiotherapy for patients with LAHNC did not reduce the incidence of pneumonias, it did reduce hospitalisation rates and episodes with fever significantly and consequently tended to be cost-effective.

Do Canadian Radiation Oncologists Consider Geriatric Assessment in the Decision-Making Process for Treatment of Patients 80 years and Older with Non-Metastatic Prostate Cancer? - National Survey.

PURPOSE: Clinical judgement may not be sufficient to detect relevant problems in older cancer patients. We investigated what Geriatric Assessment tools (GA) are used by Canadian radiation oncologists (CROs) to treat non-metastatic prostate cancer patients aged 80 years and older. METHODS: A 27-item cross-sectional survey was developed with input from a multidisciplinary team and distributed electronically to Genitourinary (GU) CROs via LimeSurvey. Survey contents included: demographics, treatment choice based on components of GA, and how GA tools are used in clinic. Descriptive statistics were used to analyze multiple-choice data, with Open-ended question being coded and analyzed for emerging themes. RESULTS: 154 GU CRO's were contacted, 44 responded (29%). Active surveillance was the choice of therapy in older low risk prostate cancer patients regardless of factors used in a GA assessment (97%). Results in intermediate and high-risk older prostate cancer patients were more heterogenous. Functional status and comorbidities were the most important factor in the decision-making-process (94%, 91%). Sixty-six percent of CROs did not use any GA tools; yet 77% felt comfortable to very comfortable treating older patients. Eighty-eight percent felt there were some to very few guidelines in helping them to treat older patients. Barriers to using GA included lack of knowledge, time, support, and resources. CONCLUSIONS: GAs are not commonly utilized by CROs. Majority of CROs felt comfortable treating older patients with prostate cancer, regardless of guidelines/evidence in this population. This may have negative implications on patient care. CROs are however open to referring patients for a formal GA.

Thyroid cancer clinical trials in the United States: Understanding trends to maximize impact.

BACKGROUND: We sought to understand thyroid cancer study modalities, publications, and grants. This provides scope, resources, and dissemination patterns to inform future directions for research and policy. METHODS: A retrospective study of thyroid cancer trials using ClinicalTrials.gov was performed. Publication and grant awards were sourced using PubMed.gov and NIH RePORTER, respectively. RESULTS: Seventy-three thyroid cancer trials were identified out of 217 000 from 1998 to 2015. Drugs were studied in 96% of all trials. Only 14% of all trials included radiation, and 4% included surgery. Only 29% of trials published their results, NIH funding was reported for 26% of trials. Total funding was $1 845 567 484 (average award: $97135131). CONCLUSION: This study is the first to prove that drug trials predominate in thyroid cancer and quantify NIH dollars awarded. Radiation and surgery are underrepresented, despite being standard of care. We recommend better balance of therapeutics and peer-reviewed reporting of positive and negative results. LEVEL OF EVIDENCE: Level 1a evidence.

Preoperative assessment of splenic involvement in patients with peritoneal carcinomatosis with CT and MR imaging.

PURPOSE: To estimate the performances of computed tomography (CT) and magnetic resonance imaging (MRI) and those of the combination of CT with MRI in the identification of splenic involvement in patients with peritoneal carcinomatosis (PC). MATERIAL AND METHOD: CT and MRI examinations of 26 patients with PC with splenic involvement and 26 patients with PC and no splenic involvement treated by total cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were reviewed. There were 32 women and 20 men with a mean age of 53.44 ± 12.22 (SD) years (range: 20-73 years). Imaging examinations were reviewed separately as three independent imaging sets (CT only, MRI only and CT with MRI) by two independent readers. A consensus was reached during a joint reading session and these results were used for determining the performances of the three imaging sets in the diagnosis of splenic involvement using surgical and histopathological findings as standard of reference. RESULTS: Splenic involvement was histologically proven in 26/52 patients (50%). There were no significant differences in sensitivity, specificity and accuracy for the diagnosis of splenic involvement between CT, MRI and CT + MRI, with respectively 84.62%, 96.15% and 90.00% for CT, 84.62%, 84.62% and 85.00% for MRI and 92.31%, 92.31% and 92.00% for CT + MRI. CONCLUSION: CT and MRI have similar sensitivities, specificites and accuracies for the diagnosis of splenic involvement in patients with PC. The combination of CT and MRI does not significantly improve the preoperative diagnosis of splenic involvement in patients with PC compared to CT only.

Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases.

BACKGROUND: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. METHODS: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. RESULTS: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. CONCLUSION: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

Addition of Definitive Radiotherapy to Chemotherapy in Patients With Newly Diagnosed Metastatic Nasopharyngeal Cancer.

Background: Management of metastatic (M1) nasopharyngeal cancer (NPC) is controversial; data suggest high overall survival (OS) rates with definitive chemoradiotherapy (CRT). Herein, we evaluated OS in patients with M1 NPC undergoing chemotherapy alone versus CRT. Methods: The National Cancer Data Base was queried for M1 NPC cases. Patients undergoing no/unknown chemotherapy and/or with unknown/nondefinitive radiotherapy (RT) doses (<60 Gy) were excluded. Logistic regression analysis ascertained clinical factors associated with RT administration. Kaplan-Meier analysis evaluated OS between both cohorts; Cox proportional hazards modeling assessed factors associated with OS. Survival was then evaluated between matched populations using inverse-probability-weighted regression adjustment. OS between groups was also measured in patients surviving ≥1 and ≥3 years to address bias from poor-prognostic subsets (eg, widely disseminated disease), and those receiving CRT ≤30 and ≤60 days of each other (surrogates for concurrent CRT) versus >30 and >60 days (sequential) of each other. Results: Of 555 patients, 296 (53%) received chemotherapy alone and 259 (47%) underwent CRT. Patients undergoing CRT more often had private insurance (P=.001) and lived in areas with higher education levels (P=.028). Median OS in the chemotherapy-only and CRT cohorts were 13.7 and 25.8 months, respectively (P<.001); differences persisted between matched populations (P<.001). On multivariate analysis, receipt of additional RT independently predicted for improved OS (P<.001). OS differences between cohorts remained apparent when evaluating patients surviving for ≥1 (P<.001) and ≥3 (P=.002) years. Patients who received concurrent or sequential CRT displayed improved OS over those receiving chemotherapy alone, for both the 30-day (P<.001) and 60-day cutoffs (P<.001). Conclusions: Patients with M1 NPC undergoing definitive RT and chemotherapy experienced higher survival than those receiving chemotherapy alone. Risk stratification and patient selection for such combined modality interventions is critical.

Effect of Thyroid-Related Symptoms on Long-Term Quality of Life in Patients with Differentiated Thyroid Carcinoma: A Population-Based Study in Sweden.

BACKGROUND: Differentiated thyroid cancer (DTC) has a good prognosis but a remaining risk of recurrence, and life-long follow-up as well as medication with levothyroxine may be necessary. The aim of this study was to clarify how thyroid-related symptoms affect health-related quality of life (HRQoL) 14-17 years after diagnosis in Swedish DTC patients. METHODS: From the all-encompassing population-based Swedish Cancer Registry, 353 patients diagnosed with DTC during 1995-1998 were identified and invited to answer a study-specific questionnaire and the HRQoL questionnaire SF-36 14-17 years after their diagnosis. Subgroups were studied according to thyroid-related symptoms, both symptoms correlated to thyroid disease or levothyroxine treatment and side effects from surgery and radioiodine treatment. RESULTS: Of the patients with DTC, 279 (79%) answered the questionnaires. In all, only 19 (7%) reported a recurrence. Patients with one single symptom (e.g., fatigue, sleeping disorders, irritability, lower stress resistance, muscle weakness, bodily restlessness, sweating, palpitations, or flushes) had significantly lower HRQoL measured with the SF-36 compared to those without that specific symptom (p < 0.001). Furthermore, those 238 patients with at least one symptom, regardless of which one, had significantly lower HRQoL in all eight SF-36 domains compared to patients that no thyroid symptom (n = 34; p < 0.001). In seven patients, the questionnaires were not complete in terms of the thyroid-related questions. The association between thyroid symptoms and lower HRQoL remained after adjusting for age, sex, comorbidities, education, and menopause. CONCLUSIONS: DTC patients reporting thyroid symptoms scored lower in HRQoL compared to those with no symptoms >14 years after diagnosis.

Efficacy of qualitative response assessment interpretation criteria at 18F-FDG PET-CT for predicting outcome in locally advanced cervical carcinoma treated with chemoradiotherapy.

OBJECTIVES: To evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome. METHODS: Ninety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test. RESULTS: Forty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4Eleven11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death (P < 0.001). CONCLUSION: Use of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced cervical carcinoma predicts survival outcome and this prognostic information may help guide further patient management.

The changing landscape of papillary thyroid cancer: Epidemiology, management, and the implications for patients.

The incidence of thyroid cancer has tripled over the past 3 decades, with the vast majority of the increase noted to be among small, indolent papillary thyroid carcinomas. Substantial overdiagnosis and potential overtreatment have led to a shift in clinical practice toward less aggressive approaches and a focus on improved risk stratification. This shift in practice may be associated with recent evidence suggesting that the increase in the incidence of thyroid cancer is slowing. Because patients are often young when they are diagnosed with thyroid cancer and because there is excellent long-term, disease-specific survival, there is an ever-growing population of survivors of thyroid cancer in the United States who accumulate substantial associated health care costs as they undergo surveillance and/or remedial treatment. Survivors of thyroid cancer can experience significant detriments to their quality of life and endure financial hardship. Future research should focus on the appropriateness of treatment as well as the financial and quality-of-life effects of thyroid cancer survivorship. Cancer 2016;122:3754-3759. © 2016 American Cancer Society.