Factors associated with the melanoma diagnostic interval in Ontario, Canada: a population-based study.

BACKGROUND: Protracted times to diagnosis of cancer can lead to increased patient anxiety, and in some cases, disease progression and worse outcomes. This study assessed the time to diagnosis for melanoma, and its variability, according to patient-, disease-, and system-level factors. METHODS: This is a descriptive, cross-sectional study in Ontario, Canada from 2007-2019. We used administrative health data to measure the diagnostic interval (DI)-and its two subintervals-the primary care subinterval (PCI) and specialist care subinterval (SCI). Multivariable quantile regression was used. RESULTS: There were 33,371 melanoma patients. The median DI was 36 days (interquartile range [IQR]: 8-85 days), median PCI 22 days (IQR: 6-54 days), and median SCI 6 days (IQR: 1-42 days). Increasing comorbidity was associated with increasing DI. Residents in the most deprived neighbourhoods and those in rural areas experienced shorter DIs and PCIs, but no differences in SCI. There was substantial variation in the DI and SCI across health regions, but limited differences in the PCI. Finally, patients with a history of non-melanoma skin cancer, and those previously established with a dermatologist experienced significantly longer DI, PCI, and SCI. DISCUSSION: This study found variability in the melanoma DI, notably by system-level factors.

Neoadjuvant chemotherapy for triple-negative and Her2 +ve breast cancer: striving for the standard of care.

PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative (TN) and Her2-positive (HER2) breast cancers is supported by international guidelines as it can decrease extent of surgery, provide prognostic information, and allow response-driven adjuvant therapies. Our goal was to describe practice patterns for patients with TN and HER2-positive breast cancer and identify the factors associated with the receipt of NAC versus surgery as initial treatment. METHODS: A retrospective population-based cohort study of adult women diagnosed with stage I-III TN or HER2-positive breast cancer (2012-2020) in Ontario was completed using linked administrative datasets. The primary outcome was NAC as first treatment. The association between NAC and patient, tumor, and practice-related factors was examined using multivariable logistic regression models. RESULTS: Of 14,653 patients included, 23.9% (n = 3500) underwent NAC as first treatment. Patients who underwent NAC were more likely to be younger and have larger tumors, node-positive disease, and stage 3 disease. Of patients who underwent surgery first, 8.8% were seen by a medical oncologist prior to surgery. On multivariable analysis, increasing tumor size (T2 vs T1/T0: 2.75 (2.31-3.28)) and node-positive (N1 vs N0: OR 3.54 (2.92-4.30)) disease were both associated increased odds of receiving NAC. CONCLUSION: A considerable proportion of patients with TN and HER2-positive breast cancer do not receive NAC as first treatment. Of those, most were not assessed by both a surgeon and medical oncologist prior to initiating therapy. This points toward potential gaps in multidisciplinary assessment and disparities in receipt of guideline-concordant care.

A Feasibility Randomized Controlled Trial of Prehabilitation During Neoadjuvant Chemotherapy for Women with Breast Cancer: A Mixed Methods Study.

BACKGROUND: Limited data exist regarding the role of multimodal prehabilitation during neoadjuvant chemotherapy (NACT) for breast cancer. Determining large trial feasibility and identifying signals of prehabilitation benefit are needed. PATIENTS AND METHODS: We conducted a randomized controlled feasibility trial of multimodal prehabilitation versus usual care during NACT among women diagnosed with non-metastatic breast cancer. Intervention participants received an individualized exercise program, dietetic support, and stress management counseling during NACT. The trial assessed feasibility via rates of recruitment, attrition, adherence, and study-related adverse events. Physical fitness (Six Minute Walk Test, grip strength, anthropometrics) and patient-reported outcomes were assessed at baseline, after NACT completion, and 6 months after surgery as exploratory outcomes, and analyzed using linear mixed effects models. Qualitative data were collected from a subsample to understand feasibility and acceptability of prehabilitation. RESULTS: A total of 72 participants were enrolled from the 123 eligible patients (recruitment rate of 53%). There was a 13% attrition rate and no intervention-related adverse events. Participants in the prehabilitation group had better 6-min walk distance at the post-chemotherapy timepoint [between group difference of 49.43 m, 95% confidence interval (CI) - 118.1, 19.2] and at the post-surgery timepoint (27.3, 95% CI -96.8, 42.2) compared with the control group. Prehabilitation participants reported better quality of life, less fatigue, and improved physical activity levels compared with usual care participants. Interviews revealed that the intervention had a positive impact on the treatment experience. CONCLUSIONS: This study demonstrated feasibility and improvement in physical and psychosocial outcomes. Larger trials assessing intervention efficacy to confirm indications of prehabilitation benefit are warranted.

Hysterectomy versus chemotherapy for low-risk non-metastatic gestational trophoblastic neoplasia (GTN): A cost-effectiveness analysis.

OBJECTIVE: Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). METHODS: A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis. RESULTS: Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality. CONCLUSION: Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN.

Low Rates of Medical Oncology Consultation for Older Women (≥ 70 Years) with Newly Diagnosed, Non-Metastatic Breast Cancer: A Population-Based Study.

BACKGROUND: Curative intent cancer treatment needs to be balanced with patient comorbidities and quality of life when treating older women with breast cancer. We examined consultation patterns and association of age at diagnosis with lack of specialist cancer consultations for older women with breast cancer. METHODS: We conducted a population-based retrospective cohort study of older women (≥ 70 years of age) with incident, non-metastatic breast cancer (2010-2018) by linking administrative databases in Ontario, Canada. The outcomes of interest were lack of specialist cancer consultation (surgeon, medical oncology, or radiation oncology) within 12 months of diagnosis. Association of age with lack of specialist cancer consultation was examined using Poisson regression modeling. RESULTS: Of 21,849 older women, 2.4% (n = 517) did not have any specialist cancer consultation within 12 months of diagnosis; lack of any specialist cancer consultation increased with age (0.8% for age 70-74 years, 1.3% for age 75-79 years, 2.5% for age 80-84 years, and 7.0% for age ≥ 85 years; p < 0.001). The proportion of patients who did not have consultations with surgeons, medical oncologists, and radiation oncologists was 8.6% (n = 1888), 34.4% (n = 7510), and 24.7% (n = 5404), respectively. Older age group was independently associated with an increased likelihood of lacking any specialist consultation, as well as not receiving surgical and medical oncology consultations. CONCLUSION: More than one-third of women ≥ 70 years of age with non-metastatic breast cancer did not have a consultation with a medical oncologist, with women aged ≥ 85 years least likely to have a medical oncology consultation.

Budget impact analysis of molecular subtype profiling in endometrial cancer.

OBJECTIVE: This study evaluated the costs associated with four approaches to classifying endometrial cancer (EC), including histomorphological, histomorphological with ancillary immunohistochemical assays, histomolecular and selective molecular classification. METHODS: Direct costs were determined per EC sample from the hospital's perspective. A budget impact analysis and sensitivity analysis were conducted to estimate the mean, minimum and maximum costs per sample and annual institutional costs in adjusted 2022 Canadian dollars. A provincial cost forecast was projected based on expected 2022 EC biopsies. RESULTS: In 2018, our institution performed 190 EC biopsies. The mean cost per biopsy was $158 ($156-$212) for histomorphological classification, $384 ($360-$514) for histomorphological classification with immunohistochemistry and $1297 ($1265-1833) for histomolecular classification. Total annual institutional cost for histomorphological classification was $29,980 and $72,950 with immunohistochemistry. For histomolecular classification, the first year cost was $246,521, accounting for initial educational learning curve, and $233,461 thereafter, assuming a consistent number of biopsies per year. Targeted implementation of histomolecular classification among high-grade, p53 abnormal and/or MMR-deficient ECs (56% of cases) cost $169,688 in the first year and $162,418 annually thereafter. With a projected 3400 EC biopsies in Ontario in 2022, histomorphological classification would annually cost $537,078 and $1,305,677 with immunohistochemistry. Histomolecular classification would cost $4,410,203 in the first year and $4,176,737 annually once established. Selective molecular classification would lead to a cost of $3,044,178 in the first year and $2,913,443 thereafter. CONCLUSIONS: The study highlights the need for informed decision-making when implementing molecular classification in clinical practice, given the substantial incremental healthcare costs associated with these approaches.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

BACKGROUND: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population. METHODS: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada. Univariable and multivariable logistic regression analyses were performed to identify predictors of SLNB positivity. RESULTS: Overall, 676 patients were analyzed. Most patients had one or more high-risk features: Breslow thickness 0.8-1 mm in 78.1% of patients, ulceration in 8.3%, mitotic rate > 1/mm2 in 42.5%, Clark's level ≥ 4 in 34.3%, lymphovascular invasion in 1.4%, nodular histology in 2.9%, and absence of tumor-infiltrating lymphocytes in 14.4%. Fifty-three patients (7.8%) had a positive SLNB. Breslow thickness and mitotic rate independently predicted SLNB positivity. The odds of positive SLNB increased by 50% for each 0.1 mm increase in thickness past 0.7 mm (95% confidence interval [CI] 1.05-2.13) and by 22% for each mitosis per mm2 (95% CI 1.06-1.41). Patients who had one excised node (vs. two or more) were three times less likely to have a positive SLNB (3.6% vs. 9.6%; odds ratio 2.9 [1.3-7.7]). CONCLUSIONS: Our international multi-institutional data confirm that Breslow thickness and mitotic rate independently predict SLNB positivity in patients with T1 melanoma. Even within this highly selected population, the number needed to diagnose is 13:1 (7.8%), indicating that more work is required to identify additional predictors of sentinel node positivity.

Incident Cancer Detection During Multiple Waves of COVID-19: The Tsunami After the Earthquake.

No population-based study exists to demonstrate the full-spectrum impact of COVID-19 on hindering incident cancer detection in a large cancer system. Building upon our previous publication in JNCCN, we conducted an updated analysis using 12 months of new data accrued in the pandemic era (extending the study period from September 26, 2020, to October 2, 2021) to demonstrate how multiple COVID-19 waves affected the weekly cancer incidence volume in Ontario, Canada, and if we have fully cleared the backlog at the end of each wave.

Relationship Between Breast and Axillary Pathologic Complete Response in Women Receiving Neoadjuvant Chemotherapy for Breast Cancer.

OBJECTIVE: We aim to delineate the relationship between breast and axillary pathologic complete response (pCR) in patients receiving neoadjuvant chemotherapy for breast cancer. METHODS: We performed a retrospective cohort study of patients with clinical T1-4N0-3M0 breast cancer receiving neoadjuvant chemotherapy followed by surgical therapy at Sunnybrook Health Sciences Centre in Toronto, Canada between 2014 and 2019. Clinicopathologic data were abstracted from the electronic medical record. Women were stratified into receptor subtypes as follows: hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-), HR+/HER2+, HR-/HER2+ and HR-/HER2- (triple negative) and compared with Fisher's exact test. Our primary outcome was to assess the positive predictive value of breast pCR for determining axillary pCR, and vice versa. RESULTS: There were 374 breast cancers, with 109 (29.1%) achieving breast pCR (ypT0/Tis). Amongst node-positive tumours achieving breast pCR, rates of associated axillary pCR (ypN0/0i+) were as follows: HR+/HER2- (2/6, 33.3%), HR+/HER2+ (12/13, 92.3%), HR-/HER2+ (15/17, 88.2%) and triple negative (15/17, 88.2%) (P = 0.02). Conversely, amongst node-positive tumours achieving axillary pCR, rates of associated breast pCR were: HR+/HER2- (2/10, 20.0%), HR+/HER2+ (12/23, 52.2%), HR-/HER2+ (15/24, 62.5%) and triple negative (15/26, 57.7%) (P = 0.1). CONCLUSIONS: Breast pCR is a strong predictor of axillary pCR in women with HER2-positive and triple-negative breast cancers. Conversely, axillary pCR is a modest predictor of breast pCR for these subtypes. There is a poor relationship between breast and axillary pCR in women with hormone receptor-positive disease. These data may inform future de-escalation of surgery in women with HER2-positive and triple-negative disease.

Medical Immunosuppression and Outcomes in Cutaneous Melanoma: A Population-Based Cohort Study.

BACKGROUND: Melanoma and the immune system are intimately related. However, the association of immunosuppressive medications (ISMs) with survival in melanoma is not well understood. The study evaluated this at a population level. METHODS: A cohort of patients with a diagnosis of invasive cutaneous melanoma (2007-2015) was identified from the Ontario Cancer Registry and linked to identify demographics, stage at diagnosis, prescription of immunosuppressive medications (both before and after diagnosis), and outcomes. The demographics of patients with and without prescriptions for ISM were compared. Patients eligible for Ontario's Drug Benefit Plan were included to ensure accurate prescription data. The primary outcome was overall survival. Cox Proportional Hazards Regression models identified factors associated with mortality, including use of ISM as a time-varying covariate. RESULTS: Of the 4954 patients with a diagnosis of cutaneous melanoma, 1601 had a prescription for ISM. The median age of the patients was 74 years. Overall, 58.4% of the patients were men (60.5% of those without ISM and 54% of those using ISM; p < 0.001). The use of oral immunosuppression was associated with an increased hazard of death (hazard ratio, 5.84; 95% confidence interval, 5.11-6.67; p < 0.0001) when control was used for age, disease stage at diagnosis, anatomic site, comorbidity, and treatment. Other factors associated with death were increasing age, male sex, increased disease stage, truncal location of primary melanoma, and inadequate treatment. In sensitivity analysis with steroid-only ISM use excluded, survival did not differ significantly (p = 0.355). CONCLUSIONS: The use of immunosuppressive steroids for melanoma is associated with worse overall survival. Use of steroids should be limited when possible.

Outcomes of Immunosuppressed Patients Who Develop Melanoma: A Population-Based Propensity-Matched Cohort Study.

INTRODUCTION: Few studies have examined outcomes in immunosuppressed patients who develop melanoma. The purpose of this study is to compare survival in immunosuppressed patients who developed melanoma with that in patients with melanoma who are not immunosuppressed. METHODS: Immunosuppressed patients were defined as having solid organ transplant, lymphoma, leukemia, or human immunodeficiency virus prior to diagnosis of melanoma. Patients with cutaneous melanoma with and without immunosuppression were identified retrospectively from the Ontario Cancer Registry (2007-2015) and linked with administrative databases to identify demographics, treatment, and outcomes. Immunosuppressed patients were matched with non-immunosuppressed patients based on age at diagnosis, sex, birth year, stage at diagnosis, and propensity score. The primary outcome was overall survival. Multivariable Cox proportional hazard regression was used to identify factors associated with survival. RESULTS: Baseline characteristics were well balanced in 218 immunosuppressed patients matched to 436 controls. Of the patients, 186 (28.4%) were female, and median age at melanoma diagnosis was 69 (interquartile range, IQR 59-78) years. Three-year overall survival (OS) was 65% for immunosuppressed patients and 79% for non-immunosuppressed patients. Melanoma was the leading cause of death for both groups. On multivariable analysis, immunosuppression was associated with increased mortality [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.30-2.23]. Adequate treatment (HR 0.36, 95% CI 0.22-0.58) and dermatologist visits either before (HR 0.52, 95% CI 0.36-0.73) or after (HR 0.61, 95% CI 0.41-0.90) melanoma diagnosis were associated with improved OS. CONCLUSIONS: Immunosuppressed patients who develop melanoma have worse outcomes when matched to non-immunosuppressed patients. This decrease in survival appears related to the underlying condition rather than diagnosis of melanoma.

Identifying opportunities to support patient-centred care for ductal carcinoma in situ: qualitative interviews with clinicians.

BACKGROUND: Women with ductal carcinoma in situ (DCIS) report poor patient-clinician communication, and long-lasting confusion and anxiety about their treatment and prognosis. Research shows that patient-centred care (PCC) improves patient experience and outcomes. Little is known about the clinician experience of delivering PCC for DCIS. This study characterized communication challenges faced by clinicians, and interventions they need to improve PCC for DCIS. METHODS: Purposive and snowball sampling were used to recruit Canadian clinicians by specialty, gender, years of experience, setting, and geographic location. Qualitative interviews were conducted by telephone. Data were analyzed using constant comparison. Findings were mapped to a cancer-specific, comprehensive PCC framework to identify opportunities for improvement. RESULTS: Clinicians described approaches they used to address the PCC domains of fostering a healing relationship, exchanging information, and addressing emotions, but do not appear to be addressing the domains of managing uncertainty, involving women in making decisions, or enabling self-management. However, many clinicians described challenges or variable practices for all PCC domains but fostering a healing relationship. Clinicians vary in describing DCIS as cancer based on personal beliefs. When exchanging information, most find it difficult to justify treatment while assuring women of a good prognosis, and feel frustrated when women remain confused despite their efforts to explain it. While they recognize confusion and anxiety among women, clinicians said that patient navigators, social workers, support groups and high-quality information specific to DCIS are lacking. Despite these challenges, clinicians said they did not need or want communication interventions. CONCLUSIONS: Findings represent currently unmet opportunities by which to help clinicians enhance PCC for DCIS, and underscore the need for supplemental information and supportive care specific to DCIS. Future research is needed to develop and test communication interventions that improve PCC for DCIS. If effective and widely implemented, this may contribute to improved care experiences and outcomes for women diagnosed with and treated for DCIS.

Nonoperative Management Versus Radical Surgery of Rectal Cancer After Neoadjuvant Therapy-Induced Clinical Complete Response: A Markov Decision Analysis.

BACKGROUND: Nonoperative management of rectal cancer was introduced for patients with clinical complete response after neoadjuvant chemoradiotherapy to avoid short- and long-term surgical morbidity related to radical resection. OBJECTIVE: The purpose of this study was to determine the expected life-years and quality-adjusted life-years for nonoperative management and radical resection of locally advanced rectal cancer after clinical complete response following neoadjuvant chemoradiotherapy. DESIGN: Markov modeling was used to simulate nonoperative management and radical surgery for a base case scenario over a 10-year time horizon. Estimates for various clinical variables were obtained after extensive literature search. Outcome was expressed in both life-years and quality-adjusted life-years. Deterministic sensitivity analyses were completed to assess the impact of variation in key parameters. SETTING: A decision model using a Markov model was designed. PATIENTS: The base case was a 65-year-old man with a distal rectal tumor who had achieved clinical complete response after neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES: Life-years and quality-adjusted life-years were measured. RESULTS: Quality-adjusted life-years (5.79 for nonoperative management vs 5.62 for radical surgery) and life-years (6.92 for nonoperative management vs 6.96 for radical surgery) were similar between nonoperative management and radical surgery. The preferred treatment strategy changed with variations in the probability of local regrowth in nonoperative management, the probability of salvage surgery for regrowth in nonoperative management, utilities associated with nonoperative management and low anterior resection, and the utility of low anterior resection syndrome. The model was not sensitive to (dis)utilities associated with stoma, chemotherapy, or postoperative morbidity and mortality. LIMITATIONS: The study was limited by assumptions inherent to modeling studies. CONCLUSIONS: Nonoperative management and radical surgery resulted in similar (quality-adjusted) life-years. Nonoperative management should therefore be considered as a reasonable treatment option. See Video Abstract at http://links.lww.com/DCR/B246. MANEJO NO-QUIRÚRGICO VERSUS CIRUGÍA RADICAL DEL CÁNCER RECTAL DESPUÉS DE LA RESPUESTA CLÍNICA COMPLETA INDUCIDA POR TERAPIA NEOADYUVANTE: UN ANÁLISIS DE DECISIÓN DE MARKOV: Se introdujo el tratamiento no quirúrgico del cáncer rectal para pacientes con respuesta clínica completa después de la quimiorradioterapia neoadyuvante para evitar la morbilidad quirúrgica a corto y largo plazo relacionada con la resección radical.Determinar los años de vida esperados y los años de vida ajustados por calidad para el tratamiento no-quirúrgico y la resección radical del cáncer rectal localmente avanzado, después de la respuesta clínica completa siguiente de la quimiorradioterapia neoadyuvante.El modelo de Markov se usó para simular el manejo no-quirúrgico y la cirugía radical para un escenario de caso base en un horizonte temporal de 10 años. Se obtuvieron estimaciones para diversas variables clínicas después de una extensa búsqueda bibliográfica. El resultado se expresó tanto en años de vida como en años de vida ajustados por calidad. Se completaron análisis determinísticos de sensibilidad para evaluar el impacto de la variación en los parámetros clave.Se diseñó un modelo de decisión utilizando un modelo de Markov.El caso base fue un hombre de 65 años con un tumor rectal distal que había logrado una respuesta clínica completa después de la quimiorradioterapia neoadyuvante.Años de vida y años de vida ajustados por calidad.Los años de vida ajustados por calidad (5.79 para el tratamiento no-quirúrgico frente a 5.62 para la cirugía radical) y los años de vida (6.92 para el tratamiento no-quirúrgico frente a 6.96 para la cirugía radical) fueron similares entre el tratamiento no-quirúrgico y la cirugía radical. La estrategia de tratamiento preferida cambió con las variaciones en la probabilidad de nuevo crecimiento local en el manejo no-operatorio, la probabilidad de cirugía de rescate para el rebrote en el manejo no-operatorio, las utilidades asociadas con el manejo no-operatorio, y la resección anterior baja y la utilidad de el syndrome de resección anterior baja. El modelo no era sensible a las (des) utilidades asociadas con el estoma, la quimioterapia o la morbilidad y mortalidad postoperatorias.El estudio estuvo limitado por suposiciones inherentes a los estudios de modelado.El manejo no-quirúrgico y la cirugía radical resultaron en años de vida similares (ajustados por calidad). Por lo tanto, el tratamiento no-quirúrgico debe considerarse como una opción de tratamiento razonable. Consulte Video Resumen en http://links.lww.com/DCR/B246.

Lesional therapies for in-transit melanoma.

BACKGROUND AND OBJECTIVES: To describe the outcomes of lesional therapy of in-transit melanoma (ITM) with interleukin-2 (IL-2), diphencyprone (DPCP), combination lesional therapy (IL-2, retinoid, and imiquimod; CLT), and imiquimod. METHODS: Data was collected for consecutive patients with ITM receiving lesional therapies from 2008 to 2018 in a retrospective review. Included patients did not have metastatic disease at time of starting on lesional therapy and were not on systemic therapy. The primary outcome was complete pathologic response (pCR). RESULTS: Of 83 patients, 57 (69%) started treatment with IL-2, 10 (12%) with DPCP, 12 (14%) with CLT, and 4 (5%) with imiquimod. pCR was achieved in 34 patients (41%) overall, including 44% starting on IL-2, 20% on DPCP, 58% on CLT, and none on imiquimod (P = .024). With a median follow-up of 45 months, cumulative one-year overall survival was 86%, with the best survival in the CLT group. Forty-eight percent experienced common terminology criteria for adverse events grade 1 or 2 toxicity. A quarter of patients on DPCP discontinued therapy due to toxicity (P = .002). CONCLUSIONS: IL-2 may be considered for the treatment of ITM with multiple or rapidly developing lesions where there would otherwise be significant morbidity with surgery, given pCR rates and toxicity.

Economic impacts of care by high-volume providers for non-curative esophagogastric cancer: a population-based analysis.

BACKGROUND: Esophagogastric cancer (EGC) is one of the deadliest and costliest malignancies to treat. Care by high-volume providers can provide better outcomes for patients with EGC. Cost implications of volume-based cancer care are unclear. We examined the cost-effectiveness of care by high-volume medical oncology providers for non-curative management of EGC. METHODS: We conducted a population-based cohort study of non-curative EGC over 2005-2017 by linking administrative datasets. High-volume was defined as ≥ 11 patients/provider/year. Healthcare costs ($USD/patient/month-survived) were computed from diagnosis to death or end of follow-up from the perspective of the healthcare system. Multivariable quantile regression examined the association between care by high-volume providers and costs. Sensitivity analyses were conducted by varying costing horizons and high-volume definitions. RESULTS: Among 7011 non-curative EGC patients, median overall survival was superior with care by high-volume providers with 7.0 (IQR 3.3-13.3) compared to 5.9 (IQR 2.6-12.1) months (p < 0.001) for low-volume providers. Median costs/patient/month-lived were lower for high-volume providers ($5518 vs. $5911; p < 0.001), owing to lower inpatient acute care costs, despite higher medication-associated and radiotherapy costs. Care by high-volume providers was independently associated with a reduction of $599 per patient/month-lived (95% confidence interval - 966 to - 331) compared to low-volume providers. The incremental cost-effectiveness ratio was - 393. Care by high-volume providers remained the dominant strategy when varying the costing horizon and the high-volume definition. CONCLUSION: Care by high-volume providers for non-curative EGC is associated with superior survival and lower healthcare costs, indicating a dominant strategy that may provide an opportunity to improve cost-effectiveness of care delivery.

Recommendations to improve patient-centred care for ductal carcinoma in situ: Qualitative focus groups with women.

BACKGROUND: Patient-centred care (PCC) improves health-care experiences and outcomes. Women with ductal carcinoma in situ (DCIS) and clinicians have reported communication difficulties. Little prior research has studied how to improve communication and PCC for DCIS. OBJECTIVE: This study explored how to achieve PCC for DCIS. DESIGN: Canadian women treated for DCIS from five provinces participated in semi-structured focus groups based on a 6-domain cancer-specific PCC framework to discuss communication about DCIS. Data were analysed using constant comparative technique. SETTING AND PARTICIPANTS: Thirty-five women aged 30 to 86 participated in five focus groups at five hospitals. RESULTS: Women said their clinicians used multiple approaches for fostering a healing relationship; however, most described an absence of desired information or behaviour to exchange information, respond to emotions, manage uncertainty, make decisions and enable self-management. Most women were confused by terminology, offered little information about the risks of progression/recurrence, uninformed about treatment benefits and risks, frustrated with lack of engagement in decision making, given little information about follow-up plans or self-care advice, and received no acknowledgement or offer of emotional support. DISCUSSION AND CONCLUSIONS: By comparing the accounts of women with DCIS to a PCC framework, we identified limitations and inconsistencies in women's lived experience of communication about DCIS, and approaches by which clinicians can more consistently achieve PCC for DCIS. Future research should develop and evaluate informational tools to support PCC for DCIS.

National consensus recommendations on patient-centered care for ductal carcinoma in situ.

PURPOSE: The purpose of this research was to generate recommendations on strategies to achieve patient-centered care (PCC) for ductal carcinoma in situ (DCIS). METHODS: Thirty clinicians (surgeons, medical/radiation oncologists, radiologists, nurses, navigators) who manage DCIS and 32 DCIS survivors aged 18 or older were nominated. Forty-six recommendations to support PCC for DCIS were derived from primary research, and rated in a two-round Delphi process from March to June 2018. RESULTS: A total of 29 clinicians and 27 women completed Round One, and 28 clinicians and 22 women completed Round Two. The 29 recommendations retained by both women and clinicians reflected the PCC domains of fostering patient-physician relationship (5), exchanging information (5), responding to emotions (1), managing uncertainty (4), making decisions (9), and enabling patient self-management (5). An additional 13 recommendations were retained by women only: fostering patient-physician relationship (1), exchanging information (3), responding to emotions (2), making decisions (3), and enabling patient self-management (4). Some recommendations refer to processes (i.e., ask questions about lifestyle or views about risks/outcomes to understand patient preferences); others to tools (i.e., communication aid). Panelists recommended a separate consensus process to refine the language that clinicians use when describing DCIS. CONCLUSIONS: This is the first study to generate guidance on how to achieve PCC for DCIS. Organizations that deliver or oversee health care can use these recommendations on PCC for DCIS to plan, evaluate, or improve services. Ongoing research is needed to develop communication tools, and establish labels and language for DCIS that optimize communication.

Squamous Cell Carcinoma with Regional Metastasis to Axilla or Groin Lymph Nodes: a Multicenter Outcome Analysis.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) of the trunk/extremities with nodal metastasis represents a rare but significant clinical challenge. Treatment patterns and outcomes are poorly described. PATIENTS AND METHODS: Patients with cSCC who developed axilla/groin lymph node metastasis and underwent curative-intent surgery between 2005 and 2015 were identified at four Canadian academic centers. Demographics, tumor characteristics, treatment patterns, recurrence rates, and mortality were described. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Predictors of survival and any recurrence were explored using Cox regression and logistic regression models, respectively. RESULTS: Of 43 patients, 70% were male (median age 74 years). Median follow-up was 38 months. Median time to nodal metastasis was 11.3 months. Thirty-one and 12 patients had nodal metastasis to the axilla and groin, respectively. A total of 72% and 7% received adjuvant and neoadjuvant radiation, respectively, while 5% received adjuvant chemotherapy. Following surgery, 26% patients developed nodal and/or distant disease recurrence. Crude mortality rate was 39.5%. Mean OS was 5.3 years [95% confidence interval (CI) 3.9-6.8 years], and 5-year OS was 55.1%. Mean DFS was 4.8 years (95% CI 3.3-6.2 years), and five-year DFS was 49.3%. Any recurrence was the only independent predictor of death [p = 0.036, odds ratio (OR) = 29.5], and extracapsular extension (p = 0.028, OR = 189) and age (p = 0.017, OR = 0.823) were independent predictors of recurrence. CONCLUSIONS: This represents the largest contemporary series to date of outcomes for patients with axilla/groin nodal metastases from cSCC. Despite aggressive treatment, outcomes remain modest, indicating the need for a continued multidisciplinary approach and integration of new systemic agents.

Locally advanced breast cancer treated with neoadjuvant chemotherapy and adjuvant radiotherapy: a retrospective cohort analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used to treat locally advanced breast cancer (LABC). Improved response to NAC correlates with better survival outcomes. The dual purpose of this study is to report recurrence and survival outcomes for LABC patients treated with NAC, surgery and adjuvant radiotherapy and to correlate these outcomes with tumour response after NAC using multiple response assessment methods. METHODS: All LABC patients treated for curative intent with NAC, surgery, and adjuvant radiotherapy at our institute between January 2009 and December 2014 were included for analysis. NAC was mostly anthracycline and taxane-based; radiotherapy consisted of 50 Gy to the breast/chest wall and regional lymph nodes. Response to NAC was categorized using synoptic pathology reports, modified-RECIST and Chevallier scores. Survival curves were generated by the Kaplan-Meier method and compared using the log-rank test. RESULTS: The cohort included 103 patients nearly equally divided between Stage II (n = 53) and Stage III (n = 50). Rates of locoregional control (LRC), recurrence-free survival (RFS), and overall survival (OS) were 99, 98, and 100% at 1 year and 89, 69 and 77% at 5 years, respectively. Responses to NAC did not correlate with LRC (p > 0.05) but did correlate with RFS and OS (p < 0.05), except that the Chevallier score did not predict RFS (p = 0.06). Using bivariate Cox modeling tumour size before (p = 0.003) and after (p < 0.001) NAC, stage group (p = 0.05), and response assessed by synoptic pathology (p = 0.05), modified-RECIST (p = 0.001), and Chevallier score (p = 0.015) all predicted for RFS. No factors predicted for LRC. CONCLUSION: Pathologic response by all tested methods correlated with improved survival but were not associated with decreased LRC.

Indications for Contralateral Prophylactic Mastectomy: A Consensus Statement Using Modified Delphi Methodology.

OBJECTIVE: To reach a consensus about contralateral prophylactic mastectomy in unilateral breast cancer. SUMMARY BACKGROUND DATA: There has been a substantial increase in the number of North American women with unilateral breast cancer undergoing a therapeutic mastectomy and a contralateral prophylactic mastectomy (CPM) either simultaneously or sequentially. The purpose of this project was to create a nationally endorsed consensus statement for CPM in women with unilateral breast cancer using modified Delphi consensus methodology. METHODS: A nationally representative expert panel of 19 general surgeons, 2 plastic surgeons, 2 medical oncologists, 2 radiation oncologists, and 1 psychologist was invited to participate in the generation of a consensus statement. Thirty-nine statements were created in 5 topic domains: predisposing risk factors for breast cancer, tumor factors, reconstruction/symmetry issues, patient factors, and miscellaneous factors. Panelists were asked to rate statements on a 7-point Likert scale. Two electronic rounds of iterative rating and feedback were anonymously completed, followed by an in-person meeting. Consensus was reached when there was at least 80% agreement. RESULTS: Our panelists did not recommend for average risk women with unilateral breast cancer. The panel recommended CPM for women with a unilateral breast cancer and previous Mantle field radiation or a BrCa1/2 gene mutation. The panel agreed that CPM could be considered by the surgeon on an individual basis for: women with unilateral breast cancer and a genetic mutation in the CHEK2/PTEN/p53/PALB2/CDH1 gene, and in women who may have significant difficulty achieving symmetry after unilateral mastectomy. CONCLUSION: Contralateral prophylactic mastectomy is rarely recommended for women with unilateral breast cancer.