Cancer incidence, stage shift and survival during the 2020 COVID-19 pandemic: A population-based study in Belgium.

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.

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Data-driven optimization of version 9 American Joint Committee on Cancer staging system for anal cancer.

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.

Clinical Outcomes of Patients with Metastatic Breast Cancer Treated with Hypo-Fractionated Liver Radiotherapy.

PURPOSE: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). METHODS: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004-2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). RESULTS: Thirty MBCa patients with 50 LM treated with 5-10 fraction RT were identified. Median follow-up was 14.6 (range 0.9-156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1-8.8 cm) and median biologically effective dose delivered was 122 (Q1-Q3; 98-174) Gy3. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). CONCLUSIONS: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC.

Survival outcomes used to generate version 9 American Joint Committee on Cancer staging system for anal cancer.

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.

Demographics, pattern of practice and clinical outcomes in rectal squamous cell carcinoma.

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.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer.

BACKGROUND: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). RESULTS: In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. CONCLUSION: Statistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Patient-Reported and Clinical Outcomes From 5-Fraction SBRT for Oligometastases: A Prospective Single-Institution Study.

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 D95 was 39.6 (standard deviation, 8.8; biological effective dose using an alpha/beta ratio of 10, 70.8) Gy. Mean planning target volume D95 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 D0.05 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.

Impact of Definitive Chemoradiation on Quality-of-Life Changes for Patients With Anal Cancer: Long-term Results of a Prospective Study.

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).

Anal Adenocarcinoma: A Rare Entity in Need of Multidisciplinary Management.

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).

Examining the Landscape of Prognostic Factors and Clinical Outcomes for Cancer Control.

Prognostic factors have important utility in various aspects of cancer surveillance, including research, patient care, and cancer control programmes. Nevertheless, there is heterogeneity in the collection of prognostic factors and outcomes data globally. This study aimed to investigate perspectives on the utility and application of prognostic factors and clinical outcomes in cancer control programmes. A qualitative phenomenology approach using expert interviews was taken to derive a rich description of the current state and future outlook of cancer prognostic factors and clinical outcomes. Individuals with expertise in this work and from various regions and institutions were invited to take part in one-on-one semi-structured interviews. Four areas related to infrastructure and funding challenges were identified by participants, including (1) data collection and access; (2) variability in data reporting, coding, and definitions; (3) limited coordination among databases; and (4) conceptualization and prioritization of meaningful prognostic factors and outcomes. Two areas were identified regarding important future priorities for cancer control: (1) global investment and intention in cancer surveillance and (2) data governance and exchange globally. Participants emphasized the need for better global collection of prognostic factors and clinical outcomes data and support for standardized data collection and data exchange practices by cancer registries.

Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy.

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour controlin silicoin several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10-5) well above levels required to completely ablate a ∼10 cm3tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.

Canadian consensus statement on the management of radioactive iodine-resistant differentiated thyroid cancer.

Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.

Population-based cancer staging for oesophageal, gastric, and pancreatic cancer 2012-2014: International Cancer Benchmarking Partnership SurvMark-2.

Cancer stage at diagnosis is important information for management and treatment of individual patients as well as in epidemiological studies to evaluate effectiveness of health care system in managing cancer patients. Population-based studies to examine international disparities on cancer survival by stage, however, has been challenging due to the lack of international standardization on recording stage information and variation in stage completeness across regions and countries. The International Cancer Benchmarking Partnership (ICBP) previously assessed the availability and comparability of staging information for colorectal, lung, female breast and ovarian cancers. Stage conversion algorithms were developed to aggregate and map all stage information into a single staging system to allow international comparison by stage at diagnosis. In this article, we developed stage conversion algorithms for three additional cancers, namely oesophageal, gastric and pancreatic cancers. We examined all stage information available, evaluated stage completeness, applied each stage conversion algorithm, and assessed the magnitude of misclassification using data from six Canadian cancer registries (Alberta, Manitoba, Newfoundland, Nova Scotia, Prince Edward Island and Saskatchewan). In addition, we discussed five recommendations for registries to improve international cancer survival comparison by stage: (a) improve collection and completeness of staging data; (b) promote a comparable definition for stage at diagnosis; (c) promote the use of a common stage classification system; (d) record versions of staging classifications and (e) use multiple data sources for valid staging data.

Evaluation of a multiparametric MRI scoring system for histopathologic treatment response following preoperative chemoradiotherapy for rectal cancer.

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.

2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer.

Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC. Methods: The specific clinical questions and topics addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of the Task Force members (authors of the guideline). Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, targeted/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 31 recommendations and 16 good practice statements. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of ATC. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with ATC.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.

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.

Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer.

BACKGROUND: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. METHODS: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. RESULTS: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2-7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4-8.9) on multivariable and IPTW sensitivity analyses. CONCLUSIONS: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.