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OBJECTIVE: We tested the usability of a patient-directed decision aid (DA), intended for patients with early stage papillary thyroid carcinoma (PTC) deciding to accept or reject adjuvant radioactive iodine (RAI) treatment. This decision is complicated by uncertainty of the medical evidence relating to potential treatment benefits. METHODS: The DA was tested by 12 thyroid cancer survivors, 7 thyroid specialty physicians, and 30 lay individuals with no history of thyroid cancer. The participants completed the System Usability Scale for human-computer interaction questionnaire. The medical knowledge of lay participants was assessed before and after DA exposure. Qualitative participant feedback was obtained by thinking aloud during DA use, as well as from interviews. RESULTS: Participants generally found the usability of the DA acceptable. The DA significantly increased medical knowledge. In spite of some physicians' concerns about disclosure of treatment controversy and evidence uncertainty, it was found to be acceptable to non-physicians. CONCLUSION: A computerized DA on RAI treatment is acceptable to physicians and non-physicians and can improve medical knowledge. PRACTICE IMPLICATIONS: In counseling patients about complex medical decisions, disclosure of uncertainty related to medical evidence may be acceptably conveyed using a DA. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic was associated with a profound decline in cancer diagnoses in 2020 in Belgium. Disruption in diagnostic and screening services and patient reluctance to visit health facilities led to fewer new cases and concerns that cancers may be diagnosed at more advanced stages and hence have poorer prognosis. Using data from mandatory cancer registration covering all of Belgium, we predicted cancer incidence, stage distribution and 1-year relative survival for 2020 using a Poisson count model over the preceding years, extrapolated to 2020 for 11 common cancer types. We compared these expected values to the observed values in 2020 to specifically quantify the impact of the COVID-19 pandemic, accounting for background trends. A significantly lower incidence was observed for cervical, prostate, head and neck, colorectal, bladder and breast cancer, with limited or no recovery of diagnoses in the second half of 2020 for these cancer types. Changes in stage distribution were observed for cervical, prostate, bladder and ovarian and fallopian tube tumours. Generally, changes in stage distribution mainly represented decline in early-stage than in late-stage tumours. One-year relative survival was lower than predicted for lung cancer and colorectal cancer. Stage shifts are hypothesised to result from alterations in access to diagnosis, potentially due to prioritisation of symptomatic patients, and patient reluctance to contact a physician. Since there were over 5000 fewer cancer diagnoses than expected by the end of 2020, it is critical to monitor incidence, stage distribution and survival for these cancers in the coming years., (© 2024 UICC.)

Introduction: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach., Methods: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan-Meier methods analyzed 5-year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings., Results: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1-2N1M0, whereas Stage IIIA was redefined as T3N0-1M0. Reevaluation of 5-year survival based on data-informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models., Conclusion: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data-driven optimization approach can be implemented for staging revisions across all disease sites moving forward., (© 2023 American Cancer Society.)

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether., (© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Aim: The aim of this study was to describe the baseline clinical features, treatment patterns and outcomes in rectal squamous cell carcinoma (SCC)., Method: This is a retrospective study of patients with rectal SCC treated at the Princess Margaret Cancer Centre (Toronto, Canada) between 1 January 1995 and 31 December 2020. Clinical factors associated with locoregional failure (LRF), distant metastases (DM), disease-free survival (DFS) and overall survival (OS), such as age, sex, HIV status, T-category, nodal status, grade and primary treatment, were investigated with univariate analysis (UVA)., Results: Twenty nine patients with rectal SCC were analysed with a median follow-up of 7.4 years (range 0.3-20.4 years). The median age at diagnosis was 52 years, with the majority presenting with clinical T3 disease or higher (n = 21, 72%) and positive regional lymph nodes (n = 16, 55%), while more than quarter of patients (28%) had metastatic disease. Definitive chemoradiation was the treatment modality of choice in more than half of all cases (n = 17, 59%) with a response rate of 100%. The 10-year cumulative incidence of LRF and DM was, respectively, 12% (95% CI 1.8%-32.9%) and 31% (95% CI: 12.0%-52.6%). The 5- and 10-year OS was 82% (95% CI 66.1%-100%). UVA revealed a trend towards an association of male gender (hazard ratio = 4.65, 95% CI 0.9%-24.1; p = 0.067) and primary surgical treatment (hazard ratio = 0.76, 95% CI 0.09-6.34; p = 0.061) with DFS., Conclusion: Definitive chemoradiation is an effective and preferred treatment for rectal SCC allowing for sphincter preservation with complete clinical response observed in all patients., (© 2022 Association of Coloproctology of Great Britain and Ireland.)

Purpose: To describe the long-term outcomes of a 5-fraction normal tissue tolerance adapted strategy for the management of oligometastases (OM)., Methods and Materials: Patients with histologically confirmed solid tumors, ≤5 extracranial metastases, suitable for a definitive approach for all metastatic lesions, at least one lesion suitable for Stereotactic Body Radiotherapy (SBRT), Eastern Coooperative Oncology Group Performance Status ≤2 were eligible. Treatment intervention was a 5-fraction (25-55 Gy) normal tissue adapted dosing strategy. The primary outcome was cumulative local progression rate at 12 months., Results: Between March 2013 and January 2018, 137 patients started SBRT. Median follow-up was 35.7 months. In addition, 107 (78%) patients had a solitary OM. The mean planning target volume D 95 was 39.6 (standard deviation, 8.8; biological effective dose using an alpha/beta ratio of 10, 70.8) Gy. Mean planning target volume D 95 was highest for lung lesions (48.7 [standard deviation, 4.7]; biological effective dose using an alpha/beta ratio of 10, 96.1) Gy but was <40 Gy for all other anatomic sites. Two grade 3 toxicities (gastrointestinal bleed) were observed with stomach D 0.05 30.3 Gy and 30.4 Gy. The cumulative local progression rate at 12 of 36 months was 16.1% (95% CI, 10-22) and 38.3% (95% CI 30-46.7); overall survival was 90% and 37%, and progression free survival was 58% and 19%, respectively. Mean symptom burden (Edmonton Symptom Assessment Total Score) worsened in patients with progressive disease (+8.8) at 12 months and was paralleled by changes in mean European Organization for Research and Treatment Quality of Life Core Questionnaire Summary Score and Global Health Quality of Life Score. Systemic therapy was initiated in 55% of patients at an average of 12.7 (standard deviation 12.4) months., Conclusions: If long-term progression free survival is the primary goal of therapy, SBRT for OM achieved this in <20% of patients attributable to a high risk of distant failure. Favorable local progression free survival is accompanied by preservation of quality of life, avoidance of symptom progression and reduced need of antineoplastic therapies at 12 months. Information on symptom burden, quality of life, as well as pattern of antineoplastic therapy use after progressive disease is useful to support conversations between patients, families, and health care providers. Strategies to improve patient selection and reduce distant progression rate remain a priority for further study., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Maintaining and improving quality of life (QOL) are important goals of anal cancer management. This disease is generally curable, with many long-term survivors., Objective: Long-term QOL after chemoradiation for patients with anal cancer was evaluated., Design: This was a prospective cohort study., Settings: This study used data from a prospective study of patients with anal cancer who were treated with chemoradiation between 2008 and 2013., Patients: Patients with anal cancer who were treated with image-guided intensity-modulated radiation therapy were included., Interventions: English-speaking patients completed European Organization for Research and Treatment of Cancer cancer-specific (C30) and site-specific (CR29) QOL questionnaires at baseline, at end of radiation, at 3 and 6 months, and then annually., Main Outcomes Measures: Long-term QOL was evaluated clinically (a change in score of ≥10 points was considered clinically significant) and statistically (using repeated-measurement analysis) by comparing the subscale scores at 1, 2, and 3 years with baseline scores. Subanalysis compared patients who received a radiation dose of 45 to 54 Gy versus 63 Gy., Results: Ninety-six patients were included (median follow-up of 56.5 months). The symptom and functional scales showed a clinically significant decline at the end of treatment with improvement by 3 months after treatment. There was a long-term statistically significant decline in dyspnea, body image, bowel embarrassment, fecal incontinence, and hair loss, and there was long-term statistically and clinically significant worsening of impotence. Higher radiation dose (63 Gy) was not associated with significantly worse QOL., Limitations: Limitations included single-institution, single-arm study design, and lack of dose reconstruction (ie, analyses were based on prescribed, rather than delivered, dose)., Conclusions: Patients with anal cancer treated with chemoradiation reported recovery of overall QOL to baseline levels. Specific symptoms remained bothersome, emphasizing the need to address and manage the chemoradiation-induced symptoms, during treatment and in the long term. See Video Abstract at http://links.lww.com/DCR/B905., Impacto De La Quimiorradiacin Definitiva En Cambios En La Calidad De Vida De Los Pacientes Con Cncer Anal Resultados a Largo Plazo De Un Estudio Prospective: ANTECEDENTES:Mantener y mejorar la calidad de vida son objetivos importantes del tratamiento del cáncer anal, ya que esta enfermedad generalmente es curable, con muchos sobrevivientes a largo plazo.OBJETIVO:Se evaluó la calidad de vida a largo plazo después de la quimiorradiación en pacientes con cáncer anal.DISEÑO:Este fue un estudio de cohorte prospectivo.ENTORNO CLINICO:Utilizamos datos de un estudio prospectivo en pacientes con cáncer anal tratados con quimiorradiación entre 2008-2013.PACIENTES:Los pacientes con cáncer anal fueron tratados con radioterapia de intensidad modulada guiada por imágenes.INTERVENCIONES:Los pacientes de habla inglesa completaron los cuestionarios de calidad de vida específicos de cáncer (C30) y específicos del sitio (CR29) de la Organización Europea para la Investigación y el Tratamiento del Cáncer al inicio, al final de la radiación, 3 y 6 meses, y luego anualmente.PRINCIPALES MEDIDAS DE RESULTADOS:Se evaluó a largo plazo la calidad de vida clínicamente (un cambio en la puntuación de ≥10 puntos se consideraron clínicamente significativo) y estadísticamente (usando análisis de medición repetida) comparando las subescalas de puntuación al 1, 2, y 3 años. Con puntuaciones de referencia. El subanálisis comparó pacientes que recibieron 45-54 Gy versus 63 Gy.RESULTADOS:Se incluyeron un total de 96 pacientes (mediana de seguimiento: 56,5 meses). La mayoría de las escalas funcionales y de síntomas mostraron una disminución clínicamente significativa al final del tratamiento con una mejoría a los 3 meses posteriores al tratamiento. Hubo una disminución estadísticamente significativa a largo plazo en disnea, imagen corporal, vergüenza intestinal, incontinencia fecal y pérdida de cabello; y hubo un empeoramiento a largo plazo estadística y clínicamente significativo en impotencia. La dosis de radiación más alta (63 Gy) no se asoció con una calidad de vida significativamente peor.LIMITACIONES:Institución única, diseño de estudio de un solo brazo y falta de recomposición de la dosis (es decir, los análisis se basan en la dosis prescrita, en lugar de la administrada).CONCLUSIÓNES:Los pacientes con cáncer anal tratados con quimiorradiación reportaron una recuperación de la QOL en general a los niveles de base. Síntomas específicos siguieron siendo molestos, lo que enfatiza la necesidad de resolver y tartar los síntomas inducidos por la quimiorradiación no solo durante el tratamiento, sino a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B905. (Traducción- Dr. Francisco M. Abarca-Rendon)., (Copyright © The ASCRS 2022.)

Background: Anal adenocarcinoma is a rare clinical entity for which the optimal management is not defined., Objective: This study aimed to describe the multidisciplinary management and outcomes of patients with anal adenocarcinoma., Design: This is a retrospective cohort study., Setting: This study was conducted at a quaternary cancer center., Patients: Men and women with anal adenocarcinoma treated between 1995 and 2016 were selected., Interventions: Fifty-two patients were treated with either chemoradiotherapy or trimodality therapy including radiation therapy, chemotherapy, and surgical resection., Main Outcome Measures: Local failure, regional failure, and distant metastasis rates were estimated using the cumulative incidence method. The Kaplan-Meier method was used to estimate progression-free survival and overall survival. The multivariable Cox proportional hazards model was used to evaluate the clinical predictors of outcome., Results: There was a higher 5-year rate of local failure in patients treated with chemoradiotherapy compared with trimodality therapy (53% vs 10%; p < 0.01). The 5-year incidence of distant metastases was 29% (trimodality therapy) versus 30% (chemoradiotherapy; p = 0.9); adjuvant chemotherapy did not reduce the incidence of distant metastases (p = 0.8). Five-year overall survival was 73% (trimodality therapy) versus 49.4% (chemoradiotherapy; p = 0.1). On multivariable analysis, factors associated with worse overall survival were treatment with chemoradiotherapy, cT3-4 category disease, and node-positive disease., Limitations: This study is limited by its small sample size and retrospective nature., Conclusions: Although treatment may continue to be tailored to individual patients, better outcomes with a trimodality therapy approach were observed. See Video Abstract at http://links.lww.com/DCR/B708.ADENOCARCINOMA ANAL: UNA ENTIDAD POCO FRECUENTE EN NECESIDAD DE UN MANEJO MULTIDISCIPLINARIO., Antecedentes: El adenocarcinoma anal es una entidad clínica poco frecuente por lo que aún no se define el manejo óptimo., Objetivo: Describir el manejo multidisciplinario y los resultados de los pacientes con adenocarcinoma anal., Diseo: Estudio de cohorte retrospectivo., Entorno Clinico: Centro de cáncer cuaternario., Pacientes: Hombres y mujeres con adenocarcinoma anal tratados entre 1995 y 2016., Intervenciones: Cincuenta y dos pacientes fueron tratados con quimiorradioterapia o terapia trimodal que incluyó: radioterapia, quimioterapia y resección quirúrgica., Principales Medidas De Valoracion: Se estimaron las tasas de falla local, falla regional y metástasis a distancia mediante el método de incidencia acumulada. Se utilizó el método de Kaplan-Meier para estimar la supervivencia libre de progresión y la supervivencia global. Los riesgos proporcionales de multivariable Cox se utilizaron para evaluar los predictores clínicos de los resultados., Resultados: Hubo una mayor tasa de falla local a cinco años en pacientes tratados con quimiorradioterapia en comparación con terapia trimodal (53% vs 10%; p < 0,01). La incidencia a cinco años de metástasis a distancia fue del 29% (terapia trimodal) versus 30% (quimiorradioterapia) (p = 0,9); la quimioterapia adyuvante no redujo la incidencia de metástasis a distancia (p = 0,8). La supervivencia global a cinco años fue del 73% (terapia trimodal) versus 49,4% (quimiorradioterapia); p = 0,1. En el análisis multivariable, los factores asociados con una peor supervivencia general fueron el tratamiento con quimiorradioterapia, enfermedad de categoría cT3-4 y enfermedad con ganglios positivos., Limitaciones: Este estudio está limitado por su pequeño tamaño de muestra y su naturaleza retrospectiva., Conclusiones: Aunque el tratamiento puede seguir adaptándose a pacientes individuales, se observaron mejores resultados con un enfoque TTM. Conslute Video Resumen en http://links.lww.com/DCR/B708. (Traducción- Dr. Francisco M. Abarca-Rendon)., (Copyright © The ASCRS 2021.)

Objective: The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population., Methods: Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome., Results: In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease., Conclusion: We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lukovic, Petrovic, Liu, Armstrong, Brierley, Tsang, Pasternak, Gomez-Hernandez, Liu, Asa and Mete.)

Purpose: To evaluate the performance of a multiparametric (mp) MRI scoring system for assessment of tumour response in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT)., Method: Fifty-nine consecutive patients with LARC who had rectal MRI before and after CRT followed by surgery were included. Two radiologists retrospectively assessed tumour response using a proposed mpMRI scoring system. Treatment response was classified as complete, near complete, partial or poor. Accuracy, sensitivity, specificity, positive predictive value and negative predictive values were calculated and inter-reader agreements were assessed. Pathologic tumour regression grade (pTRG) was the reference standard., Results: Treatment response was correctly predicted by both readers in 32.2%-40.7% of patients. Overestimation was more common than underestimation. Sensitivity, specificity, PPV and NPV for pathologic complete response (pCR) among both readers was 16.7-33.0 %, 88.7-94.2 %, 14.3-40.0 % and 92.5-94.2 % respectively. Sensitivity and PPV for both readers improved to 56.0-60.0 % and 53.6-66.7 % respectively when complete response and near complete response categories (good responders) were combined. Inter-reader agreement using the scoring system was fair (κ = 0.383). Agreement between mpMRI score and pathological tumour response was poor to fair for both readers (κ = 0.050 to 0.258) but improved when complete and near complete response categories (good responders) were combined (κ = 0.214 to 0.362)., Conclusions: Despite low agreement between radiological tumour response and pTRG, the proposed mpMRI-based scoring system appears useful in identifying good responders who may benefit from nonoperative management strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Until recently, cancer registries have only collected cancer clinical stage at diagnosis, before any therapy, and pathological stage after surgical resection, provided no treatment has been given before the surgery, but they have not collected stage data after neoadjuvant therapy (NAT). Because NAT is increasingly being used to treat a variety of tumors, it has become important to make the distinction between both the clinical and the pathological assessment without NAT and the assessment after NAT to avoid any misunderstanding of the significance of the clinical and pathological findings. It also is important that cancer registries collect data after NAT to assess response and effectiveness of this treatment approach on a population basis. The prefix y is used to denote stage after NAT. Currently, cancer registries of the American College of Surgeons' Commission on Cancer only partially collect y stage data, and data on the clinical response to NAT (yc or posttherapy clinical information) are not collected or recorded in a standardized fashion. In addition to NAT, nonoperative management after radiation and chemotherapy is being used with increasing frequency in rectal cancer and may be expanded to other treatment sites. Using examples from breast, rectal, and esophageal cancers, the pathological and imaging changes seen after NAT are reviewed to demonstrate appropriate staging., (© 2020 American Cancer Society.)

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Locally recurrent rectal cancer (LRRC) is a complex problem requiring multidisciplinary consultation and specialized surgical care. Given the paucity of published longer-term survival data, skepticism persists regarding the benefit of major extirpative surgery. We investigated ultra-long-term (~15 years) outcomes following radical resection of LRRC and sought relevant clinicopathologic prognostic variables., Methods: A cohort of 52 consecutive patients who underwent resection of LRRC at our institution between 1997 and 2005 were followed with serial exams and imaging up to the point of death, or 30/06/2019., Results: Median follow-up time was 16.5 years (9.9-18.3) for patients who were alive at last follow-up; only one patient was lost to follow-up, at 9.9 years. For the entire cohort of 52 patients, disease-specific survival (DSS) at 5, 10, and 15 years following salvage surgery was 41%, 33%, and 31%, respectively. All patients who had distant metastatic disease at the time of LRRC resection (n = 6) subsequently died of cancer, at a median of 21 months (4-46). In those without distant metastases at time of salvage surgery (n = 46), DSS at 5, 10, and 15 years was 47%, 38%, and 35%, respectively, median 60 months. Negative resection margin (R0) was independently predictive of superior outcomes. In patients with M0 disease who had R0 resection (n = 37), DSS at 5, 10 and 15 years was 58%, 47%, and 44%, respectively, median 73 months. No patient developed re-recurrence after 5.5 years., Conclusions: This study demonstrates exceptionally durable long-term cancer-free survival following salvage surgery for LRRC, indicating that cure is possible., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or funding source to declare., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum., Subjects, Materials, and Methods: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles., Results: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue., Conclusion: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer., Implications for Practice: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed., (© AlphaMed Press 2019.)

Background: The tall cell variant of papillary thyroid carcinoma (PTC) is as an aggressive histological variant. The proportion of tall cells needed to influence prognosis is debated., Methods: Patients with PTC and tall cells, defined as having a height-to-width ratio of ≥ 3:1, seen at a high-volume center between 2001 and 2015, were reviewed. Specimens were classified as (1) focal tall cell change, containing < 30% of tall cells; (2) tall cell variant, ≥ 30% of tall cells; and (3) control cases selected from infiltrative classical PTCs without adverse cytologic features. Univariate, sensitivity, and multivariate analyses were performed with persistent/recurrent disease as the primary outcome., Results: We identified 96 PTCs with focal tall cell change, 35 with the tall cell variant and 104 control cases. Factors associated with poor clinical prognosis were significantly greater in those with focal tall cell change and tall cell variants. Regarding primary outcome, hazard ratios were 2.3 (95% confidence interval [CI] 1.0-5.7) for focal tall cell change, and 3.4 (95% CI 1.2-8.7) for tall cell variants compared with controls. Five-year disease-free survival was higher for the control group (92.7%, CI 87.4-98.0) compared with focal tall cell change (76.3%, CI 66.1-86.5) and the tall cell variant (62.2%, CI 43.2-81.2). When stratified in groups consisting of tall cell proportions (< 10%, 10-19%, 20-29% and ≥ 30%), identification of ≥ 10% tall cell change was associated with worse outcome (p = 0.002)., Conclusions: PTCs with ≥ 10% tall cell change have worse prognosis than those without tall cells. Our data indicate that thyroid cancer management guidelines should consider PTCs with focal tall cell change outside of the low-risk classification.

Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was updated comparing the risk of SMNs in TC patients treated with RAI to TC patients without RAI. Six electronic databases were searched (up to March, 2018), supplemented with a hand search. Two reviewers independently screened citations, reviewed full-text papers, and critically appraised/abstracted data. Random-effects meta-analyses were conducted using crude data and data statistically adjusted for confounders. The outcomes were any SMN and specific SMNs for which sufficient data were available. Results: In total, 3506 unique electronic search citations and 93 full-text papers were examined, including 17 studies (3 systematic reviews and 14 original studies). Published knowledge syntheses were limited by inclusion of small numbers of studies, with two systematic reviews suggesting an increased risk of any SMN and one meta-analysis suggesting a reduced risk of breast SMN after RAI treatment. In a meta-analysis of crude data, the risk ratio of any SMN in RAI-treated TC patients was 0.98 ([confidence interval (CI) 0.76-1.27]; n  = 10 studies of 65,539 individuals, heterogeneity Q = 64.26, degrees of freedom [df] = 9, p  < 0.001, I 2  = 85.99). The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 ([CI 0.97-1.39]; n  = 6 studies, data from at least 11,241 TC patients, Q  = 10.86, df = 5, p  = 0.054, I 2  = 53.96). In secondary analyses examining specific SMNs, although relatively rare, the risk of subsequent leukemia was increased, but the risk of multiple myeloma was reduced in RAI-treated TC patients. There was no significant increased relative risk of breast cancer, salivary cancer, or combined hematologic malignancies according to RAI treatment status. Conclusions: The body of evidence on whether 131 I treatment of thyroid cancer is associated with the primary outcome of any SMN is highly heterogeneous and complex. More research examining the long-term risk of specific SMNs after 131 I treatment is needed.

Answer questions and earn CME/CNE This is a review of the major changes in the American Joint Committee on Cancer staging manual, eighth edition, for differentiated and anaplastic thyroid carcinoma. All patients younger than 55 years have stage I disease unless they have distant metastases, in which case, their disease is stage II. In patients aged 55 years or older, the presence of distant metastases confers stage IVB, while cases without distant metastases are further categorized based on the presence/absence of gross extrathyroidal extension, tumor size, and lymph node status. Patients aged 55 years or older whose tumor measures 4 cm or smaller (T1-T2) and is confined to the thyroid (N0, NX) have stage I disease, and those whose tumor measures greater than 4 cm and is confined to the thyroid (T3a) have stage II disease regardless of lymph node status. Patients aged 55 years or older whose tumor is confined to the thyroid and measures 4 cm or smaller (T1-T2) with any lymph node metastases present (N1a or N1b) have stage II disease. In patients who demonstrate gross extrathyroidal extension, the disease is considered stage II if only the strap muscles are grossly invaded (T3b); stage III if there is gross invasion of the subcutaneous tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a); or stage IVA if there is gross invasion of the prevertebral fascia or tumor encasing the carotid artery or internal jugular vein (T4b). The same T definitions will be used for both differentiated and anaplastic thyroid cancer, but the basic premise of the anatomic stage groups will remain the same. CA Cancer J Clin 2018;68:55-63. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Fatigue is common among cancer survivors, but fatigue in thyroid cancer (TC) survivors may be under-appreciated. This study investigated the severity and prevalence of moderate and severe fatigue in TC survivors. Potential predictive factors, including physical activity, were explored., Methods: A cross-sectional, written, self-administered TC patient survey and retrospective chart review were performed in an outpatient academic Endocrinology clinic in Toronto, Canada. The primary outcome measure was the global fatigue score measured by the Brief Fatigue Inventory (BFI). Physical activity was evaluated using the International Physical Activity Questionnaire-7 day (IPAQ-7). Predictors of BFI global fatigue score were explored in univariate analyses and a multivariable linear regression model., Results: The response rate was 63.1% (205/325). Three-quarters of the respondents were women (152/205). The mean age was 52.5 years, and the mean time since first TC surgery was 6.8 years. The mean global BFI score was 3.5 (standard deviation 2.4) out of 10 (10 is worst). The prevalence of moderate-severe fatigue (global BFI score 4.1-10 out of 10) was 41.4% (84/203). Individuals who were unemployed or unable to work due to disability reported significantly higher levels of fatigue compared to the rest of the study population, in uni-and multivariable analyses. Furthermore, increased physical activity was associated with reduced fatigue in uni- and multivariable analyses. Other socio-demographic, disease, or biochemical variables were not significantly associated with fatigue in the multivariable model., Conclusions: Moderate or severe fatigue was reported in about 4/10 TC survivors. Independent predictors of worse fatigue included unemployment and reduced physical activity.

Background: The radiotherapy (rt) volumes in anaplastic (atc) and differentiated thyroid carcinoma (dtc) are controversial., Methods: We retrospectively examined the patterns of failure after postoperative intensity-modulated rt for atc and dtc. Computed tomography images were rigidly registered with the original rt plans. Recurrences were considered in-field if more than 95% of the recurrence volume received 95% of the prescribed dose, out-of-field if less than 20% received 95% of the dose, and marginal otherwise., Results: Of 30 dtc patients, 4 developed regional recurrence: 1 being in-field (level iii), and 3 being out-of-field (all level ii). Of 5 atc patients, all 5 recurred at 7 sites: 2 recurrences being local, and 5 being regional [2 marginal (intramuscular to the digastric and sternocleidomastoid), 3 out-of-field (retropharyngeal, soft tissues near the manubrium, and lateral to the sternocleidomastoid)]., Conclusions: In dtc, locoregional recurrence is unusual after rt. Out-of-field dtc recurrences infrequently occurred in level ii. Enlarged treatment volumes to level ii must be balanced against a potentially greater risk of toxicity., Competing Interests: We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

Purpose: To investigate the relationship of pre-treatment volumetric apparent diffusion coefficient (ADC) histogram parameters with post-operative histopathologic treatment response and clinical outcomes following pre-operative chemoradiation treatment (CRT) in rectal cancer., Materials and Methods: In a Health Insurance Portability and Accountability Act compliant retrospective study, 78 rectal cancer patients treated with pre-operative CRT and rectal MRI were included. MR imaging analysis was performed using OncoTREAT (software tool). Multiple volumetric ADC histogram parameters (voxel distribution across ADC ranges, kurtosis, and skewness) were assessed. Correlation was made to post-operative pathological complete response, clinical, or radiological evidence of disease progression using the Mann-Whitney test., Results: Post CRT, 8 patients showed pathologic complete response and 13 patients showed distant disease progression. Pre-treatment mean ADC was 1.2 × 10 -3 mm 2 /s (range 0.3-1.99 × 10 -3 mm 2 /s). Mean kurtosis measured was 0.56 (range -1 to 6; SD 1.36). Mean skewness was 0.3 (range -1 to 2; SD 0.69). Skewness had significant correlation (p value = 0.006) with disease progression. The mean rectal tumor volume was 24cc (range 1cc-134cc). Pre-treatment MRI tumor volume showed significant correlation (p value = 0.013) with pathologic complete response. Mean ADC and percentage voxels distribution against ADC ranges had no significant correlation with treatment response or disease outcomes., Conclusion: Volumetric ADC histogram analysis of pre-CRT rectal cancer MRI appears promising for prediction of post-CRT complete response and disease progression.

Purpose: This study investigated thyroid cancer (TC) survivors' perceived satisfaction with and perceptions of survivorship care follow-up options., Methods: Well-differentiated TC (WDTC) patients receiving follow-up care at an academic cancer centre completed a questionnaire assessing perceived satisfaction with follow-up care involving different clinicians and mediated by the Internet (email or videoconference) and their perceptions of these follow-up options. We examined associations between patient characteristics and perceived satisfaction with follow-up care options. Qualitative responses were analysed using conventional content analysis., Results: Two hundred and two respondents completed the questionnaire (80 % response rate). The majority strongly agreed or agreed that they would be satisfied with specialist (surgeon, oncologist, or endocrinologist) follow-up (90.6 %) or a shared-care model that integrates specialists with primary care (67.5 %). One third (32 %) would be satisfied with video-based and 26 % with email-based specialist follow-up, 15 % with primary care alone. Longer time since diagnosis and health-related Internet use were associated with higher perceived satisfaction with Internet-based follow-up. Younger age was associated with higher perceived satisfaction with primary care follow-up. Qualitative responses (n = 145) revealed that survivors need reassurance they are receiving adequate care, regardless of the model or medium. Enablers to primary care and Internet-based follow-up are discussed., Conclusions: WDTC survivors want specialists involved in their follow-up. A specialist/primary care shared-care approach appears to be a suitable alternative to specialist-led follow-up for TC survivors. Internet-based visits could address some aspects of follow-up care for some WDTC survivors. Future work should examine patient and provider requirements for shared, multi-modal survivorship care.

The use of external-beam radiotherapy (EBRT) in differentiated thyroid cancer (DTC) is debated because of a lack of prospective clinical data, but recent retrospective studies have reported benefits in selected patients. The Endocrine Surgery Committee of the American Head and Neck Society provides 4 recommendations regarding EBRT for locoregional control in DTC, based on review of literature and expert opinion of the authors. (1) EBRT is recommended for patients with gross residual or unresectable locoregional disease, except for patients <45 years old with limited gross disease that is radioactive iodine (RAI)-avid. (2) EBRT should not be routinely used as adjuvant therapy after complete resection of gross disease. (3) After complete resection, EBRT may be considered in select patients >45 years old with high likelihood of microscopic residual disease and low likelihood of responding to RAI. (4) Cervical lymph node involvement alone should not be an indication for adjuvant EBRT., (© 2015 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT)., Methods and Materials: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT). Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs., Results: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86)., Conclusions: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases., Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board-approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm(3) (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm(3) gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping., Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose-response predictor than the minPTV dose., Conclusions: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose-response outcomes should increase the concordance between the planned and delivered doses., (Copyright © 2015. Published by Elsevier Inc.)

Background: Patient decision aids (P-DAs) inform medical decision making, but longer term effects are unknown. This article describes extended follow-up from a thyroid cancer treatment P-DA trial., Methods: In this single-center, parallel-design randomized controlled trial conducted at a Canadian tertiary/quaternary care center, early-stage thyroid cancer patients from a P-DA trial were contacted 15 to 23 months after randomization/radioactive iodine (RAI) decision making to evaluate longer term outcomes. It was previously reported that the use of the computerized P-DA in thyroid cancer patients considering postsurgical RAI treatment significantly improved medical knowledge in comparison with usual care alone. The P-DA and control groups were compared for the following outcomes: feeling informed about the RAI treatment choice, decision satisfaction, decision regret, cancer-related worry, and physician trust. In a subgroup of 20 participants, in-depth interviews were conducted for a qualitative analysis., Results: Ninety-five percent (70 of 74) of the original population enrolled in follow-up at a mean of 17.1 months after randomization. P-DA users perceived themselves to be significantly more 1) informed about the treatment choice (P = .008), 2) aware of options (P = .009), 3) knowledgeable about treatment benefits (P = .020), and 4) knowledgeable about treatment risks/side effects (P = .001) in comparison with controls. There were no significant group differences in decision satisfaction (P = .142), decision regret (P = .199), cancer-related worry (P = .645), mood (P = .211), or physician trust (P = .764). In the qualitative analysis, the P-DA was perceived to have increased patient knowledge and confidence in decision making., Conclusions: The P-DA improved cancer survivors' actual and long-term perceived medical knowledge with no adverse effects. More research on the long-term outcomes of P-DA use is needed., (© 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned., Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer., Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R(2)). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination., Results: The best five alternate papillary cancer systems had age cut-points of 45-50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50-55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003-0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197)., Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation.

Context: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer., Objective: The objective was to examine effects of initial therapies on outcomes., Design/setting: This was a prospective multi-institutional registry., Patients: A total of 4941 patients, median follow-up, 6 years, participated., Intervention: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST)., Main Outcome Measure: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses., Results: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P = .04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P = .049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3., Conclusions: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients.

Background: We have shown in a randomized controlled trial that a computerized patient decision aid (P-DA) improves medical knowledge and reduces decisional conflict, in early stage papillary thyroid cancer patients considering adjuvant radioactive iodine treatment. Our objectives were to examine the relationship between participants' baseline information preference style and the following: 1) quantity of detailed information obtained within the P-DA, and 2) medical knowledge., Methods: We randomized participants to exposure to a one-time viewing of a computerized P-DA (with usual care) or usual care alone. In pre-planned secondary analyses, we examined the relationship between information preference style (Miller Behavioural Style Scale, including respective monitoring [information seeking preference] and blunting [information avoidance preference] subscale scores) and the following: 1) the quantity of detailed information obtained from the P-DA (number of supplemental information clicks), and 2) medical knowledge. Spearman correlation values were calculated to quantify relationships, in the entire study population and respective study arms., Results: In the 37 P-DA users, high monitoring information preference was moderately positively correlated with higher frequency of detailed information acquisition in the P-DA (r = 0.414, p = 0.011). The monitoring subscale score weakly correlated with increased medical knowledge in the entire study population (r = 0.268, p = 0.021, N = 74), but not in the respective study arms. There were no significant associations with the blunting subscale score., Conclusions: Individual variability in information preferences may affect the process of information acquisition from computerized P-DA's. More research is needed to understand how individual information preferences may impact medical knowledge acquisition and decision-making.

Background: Well-differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web-based repository of a patient's clinical information. Ten clinical decision-making modules (CDMMs) process this information and display individualized treatment recommendations., Methods: We conducted a review of the literature and analysis of the management of patients with recurrent/persistent WDTC., Results: Surgery remains the most common treatment in recurrent/persistent WDTC and can be performed with limited morbidity in experienced hands. However, careful observation may be the recommended course in select patients. Reoperation yields biochemical remission rates between 21% and 66%. There is a reported 1.2% incidence of permanent unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism. External beam radiotherapy and percutaneous ethanol ablation have been reported as therapeutic alternatives. Radioactive iodine as a primary therapy has been reported previously for metastatic lymph nodes, but is currently advocated by the ATA as an adjuvant to surgery., Conclusion: The management of recurrent lymph nodes is a multifactorial decision and is best determined by a multidisciplinary team. The CDMMs allow for easy adoption of contemporary knowledge, making this information accessible to both patient and clinician., (© 2014 Wiley Periodicals, Inc.)

Background: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis., Objective: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry., Methods: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) or perioperative TgAb status (n=1770; the TgAb cohort) were analyzed for tumor stage, persistent disease, recurrence, and overall survival (OS; median follow-up, 5.5 years). Parametric tests assessed log-transformed TSH, and categorical variables were tested with chi square. Disease-free survival (DFS) and OS was assessed with Cox models., Results: Geometric mean serum TSH levels were higher in patients with higher-stage disease (Stage III/IV=1.48 vs. 1.02 mU/L for Stages I/II; p=0.006). The relationship persisted in those aged ≥45 years after adjusting for sex (p=0.01). Gross extrathyroidal extension (p=0.03) and presence of cervical lymph node metastases (p=0.003) were also significantly associated with higher serum TSH. Disease recurrence and all-cause mortality occurred in 37 and 38 TSH cohort patients respectively, which limited the power for survival analysis. Positive TgAb was associated with lower stage on univariate analysis (positive TgAb in 23.4% vs. 17.8% of Stage I/II vs. III/IV patients, respectively; p=0.01), although the relationship lost significance when adjusting for age and sex (p=0.34). Perioperative TgAb was not an independent predictor of DFS (hazard ratio=1.12 [95% confidence interval=0.74-1.69]) or OS (hazard ratio=0.98 [95% confidence interval=0.56-1.72])., Conclusions: Preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases. Perioperative TgAb is not an independent predictor of DTC prognosis. A larger cohort is required to assess whether preoperative serum TSH level predicts recurrence or mortality.

Purpose: Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion., Methods and Materials: Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy., Results: Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant., Conclusions: Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objective: The psychosocial impact of local-regional thyroid cancer recurrence is not known. The aim of this study was to explore thyroid cancer patients' experiences relating to diagnosis and treatment of local-regional disease recurrence., Methods: We conducted 15 semi-structured interviews with survivors of differentiated thyroid cancer who underwent neck reoperation for recurrent disease. Participants were recruited from the clinical practices of thyroid surgeons and endocrinologists at University Health Network and Mount Sinai Hospitals in Toronto, Ontario. Participant interviews were audio-recorded, transcribed verbatim, and analyzed using qualitative methods. Saturation of themes was achieved., Results: Local-regional recurrence of thyroid cancer was associated with significant psychological distress. Confidence in healthcare providers as well as psychosocial support from family or social relations, were helpful in coping with disease recurrence. After recovery from treatment, post-traumatic growth was reported. However, questions and worry about the risk for future recurrence lingered at follow-up., Conclusions: Local-regional recurrence of thyroid cancer has a significant psychosocial impact on patients, and support needs are heightened throughout the experience. Healthcare providers should strive to ensure that medical information and psychosocial needs of such patients are met, throughout the treatment experience, as well as at follow-up., (Copyright © 2013 Wiley Periodicals, Inc.)

The International Cancer Benchmarking Partnership is investigating cancer survival differences between six high-income nations using population-based cancer registry data. Differences in overall survival are often explained by differences in the stage at diagnosis and stage-specific survival. Comparing stage at diagnosis using cancer registry data is challenging because of different regional practices in defining stage, despite the existence of international staging classifications such as TNM. This paper describes how stage data may be reconciled for international analysis. Population-based cancer registry data were collected for 2.4 million adults diagnosed with colorectal, lung, breast (women) or ovarian cancer during 1995-2007 in Australia, Canada, Denmark, Norway, Sweden and the United Kingdom. The stage data received were coded to a variety of international systems, including the TNM classification, Dukes' for colorectal cancer, FIGO for ovarian cancer, and to national "localised, regional, distant" categorisations. To optimise comparability for analysis, a rigorous and repeatable process was defined to produce a final stage variable for each patient. An algorithm was also defined to map TNM, Dukes' and FIGO to a "localised, regional, distant" categorisation. We recommend how stage data should be recorded and processed to optimise comparability in population-based international comparisons of stage-specific cancer outcomes. The process we describe to produce comparable stage data forms a benchmark for future research. The algorithm to convert between TNM and a "localised, regional, distant" categorisation should be valuable for international studies, until global consensus is achieved to adhere to a single staging system like TNM., (Copyright © 2012 UICC.)

The stage of a patient's cancer at diagnosis is essential to predict the prognosis and plan the treatment. Since 2008, stage data have been collected on all Ontario patients with breast, colorectal, lung and prostate cancers and are linked to other data collected by Cancer Care Ontario. Here, an analysis of such data is presented. How it can be used to assess the value of screening programs, inform resource allocation, evaluate compliance with treatment guidelines, compare survival trends and enhance the spectrum of cancer control activities across the province is demonstrated. International comparisons can also be made., (Copyright © 2013 Longwoods Publishing.)

Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a multidisciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC., Methods: Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop., Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations., Conclusions: These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference.

Background: Esophageal adenocarcinoma has one of the fastest rising incidence rates and one of the lowest survival rates of any cancer type in the Western world. However, in many countries, trends in esophageal cancer differ according to tumour morphology and anatomical location. In Canada, incidence and survival trends for esophageal cancer subtypes are poorly known., Methods: Cancer incidence and mortality rates were obtained from the Canadian Cancer Registry, the National Cancer Incidence Reporting System and the Canadian Vital Statistics Death databases for the period from 1986 to 2006. Observed trends (annual per cent change) and five-year relative survival ratios were estimated separately for esophageal adenocarcinoma and squamous cell carcinoma, and according to location (upper, middle, or lower one-third of the esophagus). Incidence rates were projected up to the year 2026., Results: Annual age-standardized incidence rates for esophageal cancer in 2004 to 2006 were 6.1 and 1.7 per 100,000 for males and females, respectively. Esophageal adenocarcinoma incidence rose by 3.9% (males) and 3.6% (females) per year for the period 1986 to 2006, with the steepest increase in the lower one-third of the esophagus (4.8% and 5.0% per year among males and females, respectively). In contrast, squamous cell carcinoma incidence declined by 3.3% (males) and 3.2% (females) per year since the early 1990s. The five-year relative survival ratio for esophageal cancer was 13% between 2004 and 2006, approximately a 3% increase since the period from 1992 to 1994. Projected incidence rates showed increases of 40% to 50% for esophageal adenocarcinoma and decreases of 30% for squamous cell carcinoma by 2026., Discussion: Although esophageal cancer is rare in Canada, the incidence of esophageal adenocarcinoma has doubled in the past 20 years, which may reflect the increasing prevalence of obesity and gastroesophageal reflux disease. Declines in squamous cell carcinoma may be the result of the decreases in the prevalence of smoking in Canada. Given the low survival rates and the potential for further increases in incidence, esophageal adenocarcinoma warrants close attention.

Purpose: Decision-making on adjuvant radioactive iodine (RAI) treatment for early-stage papillary thyroid cancer (PTC) is complex because of uncertainties in medical evidence. Using a parallel, two-arm, randomized, controlled trial design, we examined the impact of a patient-directed computerized decision aid (DA) on the medical knowledge and decisional conflict in patients with early-stage PTC considering the choice of being treated with adjuvant RAI or not. The DA describes the rationale, possible risks and benefits, and the medical evidence uncertainty relating to the choice., Patients and Methods: We recruited 74 patients with early-stage PTC after thyroidectomy. Participants were assigned by using 1:1 central computerized randomization to either the DA group with usual care (intervention) or usual care alone (control). Medical knowledge about PTC and RAI treatment (the primary outcome), as well as decisional conflict (a secondary outcome), were measured by using validated questionnaires, and the respective scores were compared between groups., Results: Consistent with PTC epidemiology, 83.8% (62 of 74) of the participants were women, and the mean age was 45.8 years (range, 19 to 79 years). Medical knowledge about PTC and RAI treatment was significantly greater and decisional conflict was significantly reduced in the DA group compared with the control group (respective P values < .001). The use of adjuvant RAI treatment was not significantly different between groups (DA group, 11 of 37 [29.7%]; controls, seven of 37 [18.9%]; P = .278)., Conclusion: A computerized DA improves informed decision making in patients with early-stage PTC who are considering adjuvant RAI treatment. DAs are useful for patients facing decisions subject to medical evidence uncertainty.

Context: Thyroid cancer predominately affects women, carries a worse prognosis in older age, and may have higher mortality in men. Superimposed on these observations is the fact that most women have attained menopause by age 55 yr., Objective: The objective of the study was to determine whether men contribute disproportionately to papillary thyroid cancer (PTC) mortality or whether menopause affects PTC prognosis., Design: Gender-specific mortality was normalized using age-matched subjects from the U.S. population. Multivariate Cox proportional hazard regression models incorporating gender, age, and National Thyroid Cancer Treatment Cooperative Study Group stage were used to model disease-specific survival (DSS)., Participants and Setting: Patients were followed in a prospective registry., Main Outcome Measure: The relationships between gender, age, and PTC outcomes were analyzed., Results: The unadjusted hazard ratio (HR) for DSS for women was 0.40 [confidence interval (CI) 0.24-0.65]. This female advantage diminished when DSS was adjusted for age at diagnosis and stage with a HR encompassing unity (HR 0.72, CI 0.44-1.19). Additional multivariate models of DSS considering gender, disease stage, and various age groupings showed that the DSS for women diagnosed at under 55 yr was improved over men (HR 0.33, CI 0.13-0.81). However, the HR for DSS increased to become similar to men for women diagnosed at 55-69 yr (HR 1.01, CI 0.42-2.37) and at 70 yr or greater (HR 1.17, CI 0.48-2.85)., Conclusions: Although the overall outcome of women with PTC is similar to men, subgroup analysis showed that this composite outcome is composed of two periods with different outcomes. The first period is a period with better outcomes for women than men when the diagnosis occurs at younger than 55 yr; the second is a period with similar outcomes for both women and men diagnosed at ages greater than 55 yr. These data raise the question of whether an older age cutoff would improve current staging systems. We hypothesize that older age modifies the effect of gender on outcomes due to menopause-associated hormonal alterations.

Purpose: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment., Methods: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment., Results: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540)., Conclusion: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.

Surgery is the mainstay of treatment for thyroid cancer. The role for external beam radiotherapy (EBRT) as an adjuvant to surgery or as the primary therapy is established in anaplastic thyroid cancer but is controversial in differentiated thyroid cancer and uncertain in medullary thyroid cancer. This update reviews the recent reported success of combining EBRT with taxanes in anaplastic thyroid cancer. Also discussed are the recent reports from large single institutions that support the recommendations of the American and British Thyroid Associations on the use of EBRT in high-risk differentiated thyroid cancer. Further evidence on the role of EBRT in MTC is discussed. The important advances in the delivery of EBRT using intensity-modulated radiation and image-guided radiation that result in more accurate and potentially more effective radiation therapy with less toxicity are also discussed.

Purpose: To assess the movement of rectum, mesorectum, and rectal primary during a course of preoperative chemoradiotherapy., Methods and Materials: Seventeen patients with Stage II or III rectal cancer had a planning CT scan with rectal contrast before commencement of preoperative chemoradiation. The scan was repeated during Weeks 1, 3, and 5 of chemoradiation. The rectal primary (gross tumor volume), rectum, mesorectum, and bladder were contoured on all four scans. An in-house biomechanical model-based deformable image registration technique, Morfeus, was used to measure the three-dimensional spatial change in these structures after bony alignment. The required planning target volume margin for this spatial change, after bone alignment, was also calculated., Results: Rectal contrast was found to introduce a systematic error in the position of all organs compared with the noncontrast state. The largest change in structures during radiotherapy was in the anterior and posterior directions for the mesorectum and rectum and in the superior and inferior directions for the gross tumor volume. The planning target volume margins required for internal movement for the mesorectum based on the three scans acquired during treatment are 4 mm right, 5 mm left, 7 mm anterior, and 6 mm posterior. For the rectum, values were 8 mm right, 8 mm left, 8 mm anterior, and 9 mm posterior. The greatest movement of the rectum occurred in the upper third., Conclusions: Contrast is no longer used in CT simulation. Assuming bony alignment, a nonuniform margin of 8 mm anteriorly, 9 mm posteriorly, and 8 mm left and right is recommended., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines., Methods: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines., Results: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home., Conclusion: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.

In patients with early stage papillary thyroid carcinoma (PTC) who have had a thyroidectomy, the decision must be made to accept or reject radioactive iodine remnant ablation (RRA). Counselling patients about this decision can be challenging, given the medical evidence uncertainties and the complexity of related information. Although physicians are the primary source of medical information for patients considering RRA, some patients have a desire for supplemental information from sources such as the internet. Yet, thyroid cancer resources on the internet are of variable quality, and some may not be applicable to the individual case. We have developed a computerized educational tool [called a decision aid (DA)], directed to patients with early stage papillary thyroid cancer, and intended as an adjunct to physician counselling, to relay evidence-based medical information on disease prognosis and the choice to accept or reject RRA. DAs are tools used to inform patients about available treatment options and have been utilized in oncologic decision-making. We tested our web-based DA in fifty patients with early stage PTC and found that it improved medical knowledge. Furthermore, participants found the technical usability of the tool acceptable. We are currently conducting a randomized controlled trial comparing the use of the DA plus usual care to usual care alone to confirm the educational benefit of the website and examine its impact on the decision-making process. In the future, DAs may play an expanded role as an adjunct to physician counselling in the care of patients with thyroid cancer., (© 2011 Blackwell Publishing Ltd.)