Stage migration of testicular germ cell tumours in Alberta, Canada, during the COVID-19 pandemic: a retrospective cohort study.

BACKGROUND: An absence of screening recommendations and the rapid progression of testicular germ cell tumours (TGCTs) offer a perspective on the potential impact of the COVID-19 pandemic on cancer presentations. We evaluated the presenting cancer stages of TGCTs in a real-world population before and during the pandemic to assess stage migration. METHODS: We performed a retrospective review of all new patients with TGCT diagnoses in Alberta, Canada, from Dec. 31, 2018, to Apr. 30, 2021, using the Alberta Cancer Registry. Because potential changes in staging should not occur instantaneously, we used a 6-month lag time from Apr. 1, 2020, for seminomas, and a 3-month lag time for nonseminomas, to compare initial cancer stages at presentation before and during the pandemic. We evaluated monthly rates of presentation by stage and histology. Exploratory outcomes included the largest tumour dimension, tumour markers and, for advanced disease, risk category and treatment setting. RESULTS: Of 335 patients with TGCTs, 231 were diagnosed before the pandemic and 104 during the pandemic (using a lag time). In total, 18 (7.8%) patients diagnosed before the pandemic presented with stage III disease, compared to 16 (15.4%) diagnosed during the pandemic (relative risk 1.97, 95% confidence interval [CI] 1.05-3.72). We observed no significant differences for secondary outcomes. Without a lag time, the rate ratio for a stage II presentation decreased significantly during the pandemic (0.40, 95% CI 0.21-0.72). INTERPRETATION: We observed signs of TGCT stage migration during the COVID-19 pandemic, driven by a decline in stage II disease and a potential rise in stage III disease. Management of TGCTs should remain a priority, even during a global pandemic.

Selection of endometrial carcinomas for p53 immunohistochemistry based on nuclear features.

The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas (EECs). Our objectives were to test the sensitivity of tumor morphology in capturing p53 abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) risk stratification. A total of 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019-2021) were retrieved and assigned to ESGO risk groups with and without p53 status. Three pathologists reviewed the representative H&E-stained slides, predicted the p53 status, and indicated whether p53 immunohistochemistry (IHC) would be ordered. Population-based survival for endometrial carcinomas diagnosed during 2008-2016 in Alberta was obtained from the Alberta Cancer Registry. The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC1/2; N = 218, 74.6%). One hundred and fifty-two EEC1/2 (52.1% overall) were stage IA and 147 (50.3%) were low risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5 and 8.3%, respectively. The average sensitivity of predicting p53abn among observers was 83.6%. Observers requested p53 IHC for 39.4% with 98.5% sensitivity to detect p53abn (99.6% negative predictive value). Nuclear features including smudged chromatin, pleomorphism, atypical mitoses, and tumor giant cells accurately predicted p53abn. In 7/292 (2.4%), p53abn upgraded ESGO risk groups (2 to intermediate risk, 5 to high risk). EEC1/2/stage IA patients had an excellent disease-specific 5-year survival of 98.5%. Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.

No evidence of disease versus residual disease in long-term responders to first-line HER2-targeted therapy for metastatic breast cancer.

BACKGROUND: Long-term response to HER2-targeted therapies is infrequent in metastatic breast cancer (MBC). We evaluated clinical characteristics of HER2-positive MBC patients with no evidence of disease (NED) vs residual disease (RES) experiencing long-term response to first-line HER2-targeted therapy. METHODS: Patients receiving first-line chemotherapy-trastuzumab (CT) or taxane-trastuzumab-pertuzumab (THP) with response duration ≥2-fold higher than in phase II/III trials (CT [18.2 months]; THP [40.4 months]) were included. Clinical characteristics and radiographic review for NED or RES was evaluated by Cox-regression (hazard ratio; HR) or Kaplan-Meier (log-rank). Characteristics associated with NED were evaluated by logistic regression (Odds; OR). RESULTS: From 01/2005-01/2016, N = 103 (4.6%) patients were identified. In multivariate analyses, NED (N = 46) showed improved progression-free (PFS) and overall survival (OS) [p < 0.001] versus RES (N = 57), with high 5-year PFS/OS for NED (93.2%/97.4%) relative to RES (10.6%/61.3%). Premenopausal status (p = 0.006), de-novo metastases (p = 0.002), and no palliative radiotherapy (p = 0.01) were associated with NED. Overall, 6/7 (85.7%) patients with NED were alive and disease-free after discontinuing HER2 treatment (≥1 year) versus 1/17 (5.9%) with RES. CONCLUSIONS: Long-term responders with NED have better survival compared to RES. Premenopausal status and de novo metastatic disease are associated with NED. Prospective studies of HER2 therapy discontinuation with NED in MBC are warranted.

Real-World Outcomes of Oxaliplatin-Based Chemotherapy on R0 Resected Colonic Liver Metastasis.

INTRODUCTION: In resected colonic liver metastasis (CLM), randomized studies of oxaliplatin-based chemotherapy have demonstrated improvements in disease-free survival (DFS), but not overall survival (OS). Additionally, oxaliplatin regimens have not been compared to non-oxaliplatin chemotherapy. Despite limited evidence, perioperative chemotherapy is often used in the management of CLM. The primary aim of this study was to assess the impact of oxaliplatin chemotherapy regimens on OS in patients who have undergone resection of CLM in a real-world setting. PATIENTS AND METHODS: Patients who underwent resection of CLM in the provinces of Alberta and British Columbia, Canada, were identified from 1996 to 2016. Perioperative (pre- and/or post-) systemic therapy was categorized as oxaliplatin or non-oxaliplatin-based chemotherapy or no chemotherapy. The primary and secondary outcomes were OS and DFS, respectively. RESULTS: We identified 511 patients who underwent R0 resection of CLM. A significant difference in median OS was identified among the oxaliplatin, non-oxaliplatin, and no-chemotherapy groups of 100, 60, and 59 months, respectively (P = .009). In multivariate analysis, patients who received oxaliplatin regimens had a lower risk of death (hazard ratio, 0.68; 95% confidence interval, 0.51-0.92; P = .012), whereas the non-oxaliplatin chemotherapy group did not (hazard ratio, 0.88; 95% confidence interval, 0.65-1.20; P = .422) compared with no chemotherapy. CONCLUSIONS: In this multicenter, retrospective, population-based study, perioperative oxaliplatin-based chemotherapy was associated with improved OS in conjunction with R0 resection of CLM. Further studies should evaluate the optimal duration and sequencing of perioperative chemotherapy in relation to curative-intent surgical resection of CLM.

Comparison of oral versus intravenous etoposide in the management of small-cell lung cancer; A real-world, population-based study.

BACKGROUND: We looked at the utility of PO versus IV etoposide for first-line treatment in combination with a platinum agent (cisplatin/carboplatin) for Small-Cell Lung Cancer (SCLC). METHODS: Patients with SCLC in Alberta from 2008 to 2015 were identified through the registry. Patients were separated on the basis of stage; limited disease (LD) and extensive disease (ED). Chemotherapy naïve patients receiving one cycle of combination chemotherapy, route of etoposide administration, dose reductions and vital status was noted. Survival was assessed using log-rank method and Kaplan-Meyer model RESULTS: About 2066 patients were identified with SCLC. N = 762 were diagnosed with LD and n = 1264 with ED. Patient characteristics were well balanced between age and sex among the two treatment groups. LS-SCLC: No statistically significant difference in overall survival (OS) between IV versus PO Etoposide (17.5 months vs 17.9 months). More dose reductions were seen in the PO group as compared to the IV group (32.5% vs 21.9% P = 0.095). ES-SCLC: There was a nonsignificant numerical difference in OS in IV versus PO Etoposide (8.7 months vs 9.7 months P = 0.124). More dose reductions were noted in the PO group as compared to the IV group (35.3% vs 21.1%). CONCLUSION: The two dosing schemes (PO and IV) yield similar OS in ES and LS SCLC, however, patients in the PO arm did require more dose modifications. Suggesting that PO etoposide may be equivalent and lead to similar outcomes as IV, however, more toxic but saving the patients multiple visits to the chemotherapy suite. Further analyses on cost efficacy and quality of life are required.

Ovarian cancer: diagnostic accuracy and tumor types distribution in East Africa compared to North America.

BACKGROUND: Ovarian cancer is a spectrum of several histologically distinct tumor types that differ in etiology, response to therapy, and prognosis. In resource-limited settings, the diagnosis of ovarian cancer can be challenging. This study describes the distribution of ovarian cancer tumor types in East Africa as well as assessing the diagnostic accuracy by using contemporary methods. METHODS: Data from 210 women identified from the records with a diagnosis of ovarian cancer in a period of 15 years were included. Two tissue microarrays were constructed and stained with 20 antibodies relevant to ovarian cancer subtyping. An integrated diagnosis was reached by the review of full Haematoxylin and Eosin stained sections, with consideration of immunohistochemical results. The integrated diagnoses were compared with the original diagnoses, and the degree of agreement was evaluated by percentage and Kappa statistics. RESULTS: Though limited by selection bias, the results suggest lower rates of ovarian cancer in East Africa compared to a North American population from Alberta, Canada. There was a higher proportion of sex cord stromal tumors and germ cell tumors in the East African population. Diagnostic accuracy for main ovarian tumor type categories was substantial (Kappa 0.70), but only fair for specific ovarian carcinoma histotypes (Kappa 0.34). Poor Haematoxylin and Eosin stain was the main factor hindering the correct diagnosis, which was not related to tissue processing. CONCLUSIONS: In a resource-limited setting, where immunohistochemistry is not routinely carried out, diagnostic accuracy for the main categories of ovarian carcinoma is substantial and could be further improved by standardization of the basic Haematoxylin and Eosin stain.

Characterizing Urban-Rural Differences in Colon Cancer Outcomes: A Population-based Analysis Based on Travel Distance to Cancer Center.

OBJECTIVE: We aimed to explore possible drivers for urban-rural disparities in colon cancer outcomes in a single-payer health care system where all patients had access to universal health care coverage. METHODS: Patients diagnosed with stage II/III colon cancer between 2004 and 2015 in Alberta, Canada were reviewed. On the basis of postal code, patients were categorized as living in urban, rural, or suburban areas based on travel distance to the cancer center. Kaplan-Meier methods and Cox regression models assessed the associations among the area of residence, receipt of treatment, and overall survival (OS). RESULTS: Of 6163 patients identified, there were 3691, 1779, and 693 from urban, rural, and suburban areas, respectively. There was a larger proportion of younger patients (P=0.033) and left-sided colon cancers (P=0.042) in urban areas. Urban patients experienced shorter times from diagnosis to surgery (P<0.001), but longer delays from surgery to adjuvant chemotherapy (P=0.001). A significant difference in outcomes was identified among urban, rural, and suburban populations where median OS were 104, 94, and 83 months, respectively (P<0.001). In multivariate analysis, the location of residence continued to predict for worse OS in suburban (hazard ratio=1.60, 95% confidence interval: 1.24-2.07, P<0.001) and rural areas (hazard ratio=1.24, 95% confidence interval: 1.02-1.50, P=0.042), when compared with urban areas. CONCLUSIONS: In this population-based study, urban-rural differences in colon cancer survival persist, even in settings with universal health care coverage. These findings may be partly driven by a younger population with more left-sided colon cancers as well as expedited surgical intervention in urban populations, but these factors do not fully explain the disparities.

Temporal Trends in Selecting Patients for Partial Nephrectomy for Small Renal Cell Carcinomas in Alberta, Canada.

BACKGROUND: When technically feasible, partial nephrectomy (pN) is preferred over radical nephrectomy (rN) due to similar oncological control with preservation of renal function. Here, we evaluate the incorporation of pN into practice for small renal masses and examine the associated outcomes. METHODS: We included patients who had undergone either a partial or radical nephrectomy in Alberta, Canada for renal cell carcinomas with pathology tumor stage T1a between 2002 and 2014 (N=1449). Patients were excluded if they had multiple tumors or if they were on dialysis prior to nephrectomy. RESULTS: pN use increased over the duration of the study period. Patients treated after the introduction of guidelines (2007) recommending the use of pN were significantly more likely to receive a pN (OR: 2.709, 95% CI: 1.944-3.775; p<0.001) after adjusting for baseline estimated glomerular filtration rate (GFR), age, and sex. Patients who received rN were at significantly increased risk of death (HR: 1.528, 95% CI: 1.029-2.270; p=0.036) after controlling for baseline GFR, age, and sex. Baseline GFR significantly affected odds of receiving pN (p<0.050) in the entire cohort, but subgroup analysis of more recently diagnosed patients (2011-2014) showed that only patients with kidney failure (GFR <15) were less likely to have received pN. DISCUSSION: The utilization of pN for patients with pT1a renal cell carcinoma has increased significantly over time and has been accelerated by the introduction of guideline recommendations. Patients treated with pN over the study period had superior overall survival.

Unwarranted imaging for distant metastases in patients with newly diagnosed ductal carcinoma in situ and stage I and II breast cancer

Background: In 2012, the American Society of Clinical Oncology (ASCO) released a Choosing Wisely Top Five list that included a recommendation against ordering advanced imaging tests to screen for metastases among asymptomatic patients with early breast cancer. Our provincial breast cancer staging guideline was subsequently updated. We report on the use of unwarranted bone scanning (BS), computed tomography (CT), nonbreast magnetic resonance imaging (MRI) and positron emission tomography (PET) among women diagnosed with stage 0­II breast cancer in Alberta in 2011­2015. Methods: The cohort was retrospectively ascertained from the Alberta Cancer Registry. We used additional provincial data sources to obtain information about diagnostic imaging tests completed from biopsy to surgical date plus 4 months. The reason for each BS, CT, MRI and PET was abstracted. We calculated the frequency of advanced imaging tests completed for routine metastatic screening. Results: Of 10 142 patients included, 2887 (28.5%) had at least 1 advanced imaging test completed for routine metastatic screening. Of these 2887 patients, 438 (15.2%) had a follow-up BS, CT, MRI or PET, and 28 patients (1.0%) had a nonbreast imageguided biopsy. Use of routine advanced imaging tests did not change clearly over time. Conclusion: Our results demonstrate persistent use of advanced imaging tests for routine metastatic screening among patients with stage 0­II breast cancer despite the release of the ASCO Choosing Wisely recommendations and the update of our provincial breast cancer staging guideline. Investigation of strategies for guideline translation to improve upon value-based care of patients with early breast cancer is warranted.

Contexte: En 2012, l'American Society of Clinical Oncology (ASCO) a publié sa liste de 5 interventions à « Choisir avec soin ¼, dans laquelle elle recommandait notamment de ne pas recourir aux techniques d'imagerie de pointe pour le dépistage des métastases chez les patientes atteintes d'un cancer du sein peu avancé et asymptomatique. Nos lignes directrices provinciales pour la stadification du cancer du sein ont été mises à jour en conséquence. Nous faisons aujourd'hui état de l'utilisation injustifiée de la scintigraphie osseuse (SO), de la tomodensitométrie (TDM), de l'imagerie par résonnance magnétique (IRM) non mammaire et de la tomographie par émission de positrons (TEP) chez les femmes ayant reçu un diagnostic de cancer du sein peu avancé (stade 0-II) en Alberta entre 2011 et 2015. Méthodes: La cohorte a été réunie de manière rétrospective à partir du registre albertain du cancer. Nous avons utilisé d'autres sources de données provinciales pour obtenir des renseignements sur les épreuves d'imagerie diagnostique effectuées entre les dates de la biopsie et les dates de la chirurgie plus 4 mois. Le motif invoqué pour recourir à chaque SO, TDM, IRM et TEP a été recueilli. Nous avons calculé la fréquence des épreuves d'imagerie de pointe effectuées pour un dépistage de routine des métastases. Résultats: Sur les 10 142 patientes incluses, 2887 (28,5 %) avaient subi au moins 1 épreuve d'imagerie de pointe pour le dépistage de routine des métastases. Parmi ces 2887 patientes, 438 (15,2 %) ont subi une SO, une TDM, une IRM ou une TEP de suivi et 28 patientes (1,0 %) ont subi une biopsie non mammaire guidée par l'imagerie. L'utilisation de routine des épreuves d'imagerie de pointe n'a pas nettement changé avec le temps. Conclusion: Selon nos résultats, l'utilisation des épreuves d'imagerie de pointe pour le dépistage de routine des métastases persiste chez les patientes atteintes d'un cancer du sein de stade 0­II, malgré la publication des recommandations Choisir avec soin de l'ASCO et la mise à jour de nos lignes directrices provinciales concernant la stadification du cancer du sein. Il faudra se pencher sur des stratégies pour améliorer l'adoption de lignes directrices relatives aux soins véritablement utiles pour les patientes atteintes d'un cancer du sein peu avancé.

Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer.

BACKGROUND: Reductions in adjuvant chemotherapy dose <85% for historical regimens (ie, cyclophosphamide/methotrexate/fluorouracil) are known to affect breast cancer survival. This threshold, in addition to early versus late dose reductions, are poorly defined for third-generation anthracycline/taxane-based chemotherapy. In patients with breast cancer receiving adjuvant 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-D), we evaluated the impact of chemotherapy total cumulative dose (TCD), and early (FEC) versus late (D only) dose reductions, on survival outcomes. PATIENTS AND METHODS: Women with stage I-III, hormone receptor-positive/negative, HER2-negative breast cancer treated with adjuvant FEC-D chemotherapy from 2007 through 2014 in Alberta, Canada, were included. TCD for cycles 1 to 6 of <85% or ≥85% was calculated. Average cumulative dose was also calculated for early (cycles 1-3) and late (cycles 4-6) chemotherapy. Survival outcomes (disease-free survival [DFS] and overall survival [OS]) were estimated using Kaplan-Meier and multivariate analysis. Cohorts were evaluated for uniformity. RESULTS: Characteristics were reasonably balanced for all cohorts. Overall, 1,302 patients were evaluated for dose reductions, with 16% being reduced <85% (n=202) relative to ≥85% (n=1,100; 84%). Patients who received TCD ≥85% relative to <85% had superior 5-year DFS (P=.025) and OS (P<.001) according to Kaplan-Meier analysis, which remained significant on univariate and multivariate analyses. In stratified late and early dose reduction cohorts, DFS and OS showed a significant inferior survival trend for dose reduction early in treatment administration in 5-year Kaplan-Meier (P=.002 and P<.001, respectively) and multivariate analyses (hazard ratio [HR], 1.46; P=.073, and HR, 1.77; P=.011, respectively). Dose delays of <14 or ≥14 days and granulocyte colony-stimulating factor use did not affect outcomes. CONCLUSIONS: Chemotherapy TCD <85% for adjuvant FEC-D affects breast cancer survival. Late reductions (D only) were not shown to adversely affect DFS or OS. Conversely, early reductions (FEC±D) negatively affected patient outcomes.

Real-World Outcomes of Adjuvant Chemotherapy for Node-Negative and Node-Positive HER2-Positive Breast Cancer.

Background: Comparative real-world outcomes for patients with HER2-positive (HER2+) breast cancer receiving adjuvant trastuzumab outside of clinical trials are lacking. This study sought to retrospectively characterize outcomes for patients with node-negative and node-positive breast cancer receiving adjuvant trastuzumab in combination with docetaxel/cyclophosphamide (DCH), docetaxel/carboplatin/trastuzumab (TCH), or fluorouracil/epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (FEC-DH) chemotherapy in Alberta, Canada, from 2007 through 2014. Methods: Disease-free survival and overall survival (OS) analyses for node-negative cohorts receiving DCH (n=111) or TCH (n=371) and node-positive cohorts receiving FEC-DH (n=146) or TCH (n=315) were compared using chi-square, Kaplan-Meier, or Cox multivariable analysis where appropriate. Results: Median follow-up was similar in node-negative (63.9 months) and node-positive (69.0 months) cohorts. The 5-year OS rates in patients with node-negative disease receiving DCH or TCH were similar (95.2% vs 96.9%; P=.268), whereas 5-year OS rates were higher but nonsignificant for patients with node-positive disease treated with FEC-DH compared with TCH (95.2% vs 91.4%; P=.160). Subgroup analysis of node-positive cohorts showed significantly improved OS with FEC-DH versus TCH in patients with estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer (98.3% vs 91.6%, respectively; P=.014). Conversely, patients with ER/PR-negative disease showed a nonsignificant trend toward higher OS rates with TCH versus FEC-DH (91.6% vs 83.3%, respectively; P=.298). Given the retrospective design, we were unable to capture all potential covariates that may have impacted treatment assignment and/or outcomes. Furthermore, cardiac toxicity data were unavailable. Conclusions: Survival rates of patients with HER2+ breast cancer in our study are comparable to those seen in clinical trials. Our findings support chemotherapy de-escalation in patients with node-negative disease and validate the efficacy of FEC-DH in those with node-positive disease.

An audit of referral and treatment patterns of high-risk prostate cancer patients in Alberta.

INTRODUCTION: We aimed to determine the impact of clinical practice guidelines (CPG) on rates of radiation oncologist (RO) referral, androgen-deprivation therapy (ADT), radiation therapy (RT), and radical prostatectomy (RP) in patients with high-risk prostate cancer (HR-PCa). METHODS: All men >18 years, diagnosed with PCa in 2005 and 2012 were identified from the Alberta Cancer Registry. Patient age, aggregated clinical risk group (ACRG) score, Gleason score (GS), pre-treatment prostate-specific antigen (PSA), RO referral, and treatment received were extracted from electronic medical records. Logistic regression modelling was used to examine associations between RO referral rates and relevant factors. RESULTS: HR-PCa was diagnosed in 261 of 1792 patients in 2005 and 435 of 2148 in 2012. Median age and ACRG scores were similar in both years (p>0.05). The rate of patients with PSA >20 were 67% and 57% in 2005 and 2012, respectively (p=0.004). GS ≤6 was found in 13% vs. 5% of patients, GS 7 in 27% vs. 24%, and GS ≥8 in 59% vs. 71% in 2005 and 2012, respectively (p<0.001). In 2005, RO referral rate was 68% compared to 56% in 2012 (p=0.001), use of RT + ADT was 53% compared to 32% (p<0.001), and RP rate was 9% vs. 17% (p=0.002). On regression analysis, older age, 2012 year of diagnosis and higher PSA were associated with decreased RO referral rates (odds ratios [OR] 0.49, 95% confidence interval [CI] 0.39-0.61; OR 0.51, 95% CI 0.34-0.76; and OR 0.64, 95% CI 0.39-0.61), respectively [p<0.001]). CONCLUSIONS: Since CPG creation in 2005, RO referral rates and ADT + RT use declined and RP rates increased, which demonstrates a need to improve adherence to CPG in the HR-PCa population.

Comparative effectiveness analysis of different salvage therapy intensities used for diffuse large B-cell lymphoma in Northern or Southern Alberta: an instrumental variable analysis.

To date, no clinical trial has addressed salvage therapy intensity for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We sought to determine whether the more intensive salvage chemotherapy approach used in Southern Alberta (SAB) compared to the conventional dose salvage approach used in Northern Alberta (NAB) affects the rates of autologous stem cell transplant (ASCT) and survival in patients with relapsed DLBCL. Using instrumental variable analysis, we examined 147 consecutive patients with relapsed/refractory DLBCL from 2004 to 2010 who received salvage therapy in SAB (n = 70) or NAB (n = 77). Patients treated in SAB had higher rates of: salvage chemotherapy response (85.0% vs. 54.0%, p = 0.001), ASCT (61.4% vs. 41.6%, p = 0.016) and 4-year overall survival (41% vs. 20%, p = 0.002) than those in NAB, respectively. This study supports the hypothesis that selective use of intensive salvage chemotherapy leads to higher rates of ASCT and survival in this population.