Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery.

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations-the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P =0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P =0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival ( P =0.103) or progression-free survival ( P =0.240) at 5 yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17-0.89; P =0.025)] but not overall survival ( P =0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.

Perspectives of health care providers referring patients to a newly implemented sexual health program in a Canadian cancer center.

PURPOSE: Screening and discussion about sexual health concerns within cancer care are frequently impeded by lack of access to sexual health resources and lack of fluency with sexual health topics. To address this, a multi-disciplinary sexual health program was developed and piloted in a Canadian tertiary cancer center. The aim of this study was to assess referring health care providers' perspectives on the newly implemented oncology sexual health program. METHODS: A brief online survey was administered system-wide to cancer care providers to query their perceptions of the pilot multidisciplinary sexual health program, the Oncology and Sexuality, Intimacy and Survivorship (OASIS) program. RESULTS: According to survey results, the OASIS program was perceived by health care providers as valuable, helpful for patients, and important for addressing gaps in clinical care. Additional comments indicated an ongoing need for increased access to information about the program and referral procedures. CONCLUSION: Survey results highlight the need for consistent program dissemination efforts to equip health care providers with accessible patient education materials and easily implemented referral procedures. Importantly, providers indicated that they were more likely to raise the topic of sexuality with patients because they had somewhere to refer patients who had sexual concerns. Overall, findings inform efforts to implement sexual health programming within cancer care institutions.

The Oncology and Sexuality, Intimacy, and Survivorship Program Model: An Integrated, Multi-disciplinary Model of Sexual Health Care within Oncology.

Cancer-related sexual dysfunction is documented as one of the most distressing and long-lasting survivorship concerns of cancer patients. Canadian cancer patients routinely report sexuality concerns and difficulty getting help. In response to this gap in care, clinical practice guidelines were recently published in the Journal of Clinical Oncology. A sweeping trend is the creation of specialized clinics for patients' sexual health concerns. However, this much-needed attempt to address this service gap can be difficult to sustain without addressing the cancer care system from a broader perspective. Herein, we describe the implementation of a tiered systemic model of cancer-related sexual health programming in a tertiary cancer center. This program follows the Permission, Limited Information, Specific Suggestions, Intensive Therapy (PLISSIT) model, used previously for guiding individual practitioners. Visually, the model resembles a pyramid. The top 2 levels, corresponding to Intensive Therapy and Specific Suggestions, are comprised of group-based interventions for common cancer-related sexual concerns and a multi-disciplinary clinic for patients with complex concerns. The bottom 2 levels, corresponding to Permission and Limited Information, consist of patient education and provider education and consultation services. We describe lessons learned during the development and implementation of this program, including the necessity for group-based services to prevent inundation of referrals to the specialized clinic, and the observation that creating specialized resources also increased the likelihood that providers would inquire about patients' sexual concerns. Such lessons suggest that successful sexual health programming requires services from a systemic approach to increase sustainability.

PIK3CA mutation and CNV status and post-chemoradiotherapy survival in patients with cervical cancer.

PURPOSE: This study aimed to describe the prognostic value of PI3K/AKT pathway mutations in a large cohort of patients with cervical cancer. EXPERIMENTAL DESIGN: Patients with pre-treatment archival specimens, diagnosed with FIGO stages IB-IVA cervical cancer between 1998 and 2014 and treated with radical, curative intent chemoradiotherapy (CRT) at a single center were identified. Mutational status was determined by next generation sequencing and PIK3CA copy number (CNV) was assessed by digital PCR. RESULTS: 190 patients with available pre-treatment tumor specimens were identified. Median OS and PFS were 57.4 and 46.0 months, respectively. A total of 161 tumors were successfully sequenced; 60 (37.3%) had PI3K/AKT pathway mutations, with 50 (30.1%) having PIK3CA hotspot mutations. PIK3CA CNV gain was noted in 79 (59.2%) of the 154 successfully analyzed. On univariate analysis, PIK3CA mutation was associated with poor OS (HR 1.73; 95% CI: 1.03-2.92; p = .037) but not PFS (HR 1.38; 0.84-2.28; p = .204). Absence of any PI3K/AKT pathway mutation was associated with improved OS (HR 1.68; 1.01-2.81; p = .046) but not PFS (HR 1.50; 0.93-2.43; p = .202). Associations were not maintained when adjusting for clinical factors. On univariate analysis, PIK3CA mutation positive, CNV normal tumors were associated with poorer OS (HR 2.55; 1.18-5.50; p = .017) and trend to worse PFS (HR 1.87; 0.90-3.83; p = .094) when compared to those with CNV gain and wildtype PIK3CA. CONCLUSIONS: PI3K/AKT pathway mutations are common in cervical cancer. Consideration of PIK3CA mutational status with CNV status may be important in predicting outcome in cervical cancer patients.

Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8+ T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8+ T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8+ T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.

Advances and Concepts in Cervical Cancer Trials: A Road Map for the Future.

OBJECTIVE: Cervical cancer is responsible for more than a quarter of a million deaths globally each year, mostly in developing countries, making therapeutic advances in all health care settings a top priority. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaboration of leading national research groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representation from the GCIG groups and selected large sites in low- and middle-income countries. METHODS: The focus was to develop a consensus on several concepts for future clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps in need of new evidence, validating control arms for present and future clinical trials and identifying national and international barriers for studies of cervix cancers. The second half of the meeting was concerned with achieving consensus on a path forward. RESULTS AND CONCLUSIONS: There were 5 principal outcomes as follows: first, a proposal to expand fertility-preserving options with neoadjuvant chemotherapy; second, validation of the assessment of sentinel lymph nodes using minimally invasive surgery with an emphasis on identification and management of low-volume metastasis, such as isolated tumor cells and micrometastasis; third, evaluation of hypofractionation for palliative and curative radiation under the umbrella of the GCIG Cervix Cancer Research Network; fourth, adding to the advances in antiangiogenesis therapy in the setting of metastatic disease; and fifth, developing a maintenance study among women at high risk of relapse. The latter 2 systemic interventions could study PI3K (phosphatidylinositol-3-kinase) inhibitors, immunotherapy, anti-human papillomavirus approaches, or novel antiangiogenic agents/combinations.

PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma.

OBJECTIVE: To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas. METHODS: We assessed PIK3CA mutational status in exon 9 and exon 20 hot spots by Sanger sequencing of DNA derived from formalin fixed paraffin embedded tissue of 57 grade 3 endometrioid, 26 serous, 11 clear cell and 5 dedifferentiated carcinomas. We correlated PIK3CA mutation status with clinicopathological and other molecular parameters. Univariate and multivariate disease specific survival analysis was performed using Kaplan-Meier and Cox regression analyses. RESULTS: PIK3CA exon 9 or exon 20 missense mutations were identified in 20 of 99 (20%) high-grade endometrial carcinomas without significant difference across histological types (p=0.22). Presence of PIK3CA exon 9 or exon 20 missense mutations was associated with shorter disease specific survival within grade 3 endometrioid (p=0.0029) but not endometrial serous (p=0.57) carcinoma based on univariate analysis. Within grade 3 endometrioid carcinoma, PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p=0.0058) and showed loss of ARID1A expression (p=0.037). CONCLUSIONS: PIK3CA exon 9 or exon 20 missense mutations are present across all histological types of high-grade endometrial carcinomas but a significant outcome association is only seen in grade 3 endometrioid carcinoma, suggesting a greater biological importance in this tumor type.

Evaluation of a National Radiation Oncology Research and Mentorship Program.

PURPOSE: The Canadian Association of Radiation Oncology Annual Scientific Meeting Medical Student Research and Mentorship Award was established in 2020 to support medical students pursuing radiation oncology (RO) research and RO as a career. This study is an evaluation of the effect of this national research and mentorship award on medical students, resident mentors, and research supervisors over 3 iterations. METHODS AND MATERIALS: Three separate surveys were created for medical student mentees, RO resident mentors, and attending research supervisors. These surveys were developed using best practice strategies for medical education surveys and circulated for peer review among experts in oncology medical education. The surveys were sent to the 52 individuals (18 students, 18 residents, 16 supervisors) who participated in 3 cycles of Canadian Association of Radiation Oncology ASM MSRMA (2020-21, 2021-22, 2022-23). After anonymization, quantitative answers were analyzed using descriptive statistics, and narrative responses were evaluated using a grounded theory approach. RESULTS: There was a 90% survey response rate. For medical student mentees, the award maintained (71%) or increased (24%) interest in pursuing an RO career. Students reported receiving helpful tips for residency applications and insight into RO residency, research, and career planning advice. Only the first student cohort currently has matching results for residency, with approximately 50% matching to RO. All resident mentor respondents felt the program either maintained or increased motivation to mentor students in RO. Research project supervisors unanimously enjoyed their role in this program and would recommend and participate in this program again. CONCLUSIONS: A national research and mentorship award for medical students has shown a positive effect on participants. Medical students felt this award program motivated them to continue pursuing oncology research and a potential career in RO. The program also enhanced mentorship skills in residents and research supervisors, which encourages further RO mentorship, teaching, and exposure for future generations of students.

Prospective validation of a machine learning model for applicator and hybrid interstitial needle selection in high-dose-rate (HDR) cervical brachytherapy.

PURPOSE: To Demonstrate the clinical validation of a machine learning (ML) model for applicator and interstitial needle prediction in gynecologic brachytherapy through a prospective clinical study in a single institution. METHODS: The study included cervical cancer patients receiving high-dose-rate brachytherapy using intracavitary (IC) or hybrid interstitial (IC/IS) applicators. For each patient, the primary radiation oncologist contoured the high-risk clinical target volume on a pre-brachytherapy MRI, indicated the approximate applicator location, and made a clinical determination of the first fraction applicator. A pre-trained ML model predicted the applicator and IC/IS needle arrangement using tumor geometry. Following the first fraction, ML and radiation oncologist predictions were compared and a replanning study determined the applicator providing optimal organ-at-risk (OAR) dosimetry. The ML-predicted applicator and needle arrangement and the clinical determination were compared to this dosimetric ground truth. RESULTS: Ten patients were accrued from December 2020 to October 2022. Compared to the dosimetrically optimal applicator, both the radiation oncologist and ML had an accuracy of 70%. ML demonstrated better identification of patients requiring IC/IS applicators and provided balanced IC and IC/IS predictions. The needle selection model achieved an average accuracy of 82.5%. ML-predicted needle arrangements matched or improved plan quality when compared to clinically selected arrangements. Overall, ML predictions led to an average total improvement of 2.0 Gy to OAR doses over three treatment fractions when compared to clinical predictions. CONCLUSION: In the context of a single institution study, the presented ML model demonstrates valuable decision-support for the applicator and needle selection process with the potential to provide improved dosimetry. Future work will include a multi-center study to assess generalizability.

A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy.

PURPOSE: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). METHODS: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). RESULTS: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. CONCLUSIONS: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy.

OBJECTIVE: Mutational activation of PIK3CA is associated with poor prognosis in patients with solid tumors, and may predict favorable response to PI3K/AKT/mTOR pathway inhibitors. However, PIK3CA mutational status has not previously been evaluated in patients with cervical carcinoma treated with radical chemoradiotherapy (CRT). The aims of this study were (1) to evaluate the frequency of PIK3CA mutations in patients with cervical cancer treated with radical CRT and (2) to examine the effect of tumor PIK3CA mutational status in pre-treatment biopsies on overall survival (OS) and progression-free survival (PFS). METHODS: Patients with cervical cancer, treated at a single institution with radical CRT, from 1999 to 2008, were eligible for this retrospective study. Pre-treatment tumor biopsies (n=157) were retrieved. Genomic DNA was extracted from tumor blocks, and exons 9 and 20 of the PIK3CA gene were sequenced for mutations. RESULTS: Eighty-two tumors were sequenced for both exon 9 and exon 20. 19/82 (23%) tumors were PIK3CA mutation positive; of these 84% were squamous cell carcinomas. 79% of mutations were in exon 9. PIK3CA mutation status was strongly associated with overall survival (OS) in FIGO stage IB/II patients, unadjusted HR 6.0 (95% CI 2.1-17.5), p=0.0002, but not stage III/IVA patients, unadjusted HR 1.0 (95% CI 0.32-3.1), p=0.98. CONCLUSIONS: In cervical cancer patients treated with CRT, tumor PIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers. Further evaluation with a larger dataset will be required to validate these findings to inform potential clinical trials designs involving PI3K/AKT/mTOR pathway inhibitors.

The prognostic significance of pretreatment leukocytosis in patients with anal cancer treated with radical chemoradiotherapy or radiotherapy.

BACKGROUND: There are emerging data showing the prognostic significance of pretreatment leukocytosis in patients with cervical cancer; it is generally associated with adverse outcome. However, the prognostic impact of leukocytosis in patients with anal cancer has not been previously reported. OBJECTIVE: The purpose of this study was to assess the relationship between pretreatment leukocytosis and clinical outcomes in patients with anal cancer treated with radical chemoradiotherapy or radiotherapy. DESIGN: This is a retrospective cohort study. SETTING AND PATIENTS: One hundred twenty-six patients with invasive anal canal cancer, treated with radical chemoradiotherapy or radiotherapy between 2000 and 2008 at 2 major tertiary cancer centers, were evaluated. MAIN OUTCOME MEASURES: The primary outcomes were disease-free and overall survival. RESULTS: Median follow-up was 24 months. Pretreatment leukocytosis (white blood cell count >10 × 10/L) was identified in 15.9% (20/126) of patients. After adjusting for sex, tumor size, and stage in a multivariate analysis, leukocytosis remained significantly associated with worse disease-free survival (HR, 2.2; 95% CI, 1.1-4.8; p = 0.045) and worse overall survival (HR, 2.9; 95% CI, 1.1-7.9; p = 0.036). Patients with both leukocytosis and anemia (pretreatment hemoglobin <125 g/L) had the worst prognosis: 2-year disease-free survival 42.1% versus 72.9% for patients without these factors (HR, 2.7; 95% CI, 1.1-6.8; p = 0.033); 2-year overall survival 60.9% versus 89.8% (HR, 4.5; 95% CI, 1.5-13.2; p = 0.006). LIMITATIONS: The study was limited by its retrospective nature and lack of patients with multiple hematologic abnormalities (ie, both anemia and leukocytosis). HIV status was unable to be evaluated. CONCLUSIONS: Pretreatment leukocytosis in patients with anal cancer is associated with significantly worse disease-free and overall survival, which appears to be exacerbated with the presence of pretreatment anemia.

COX-2 expression and survival in patients with locally advanced cervical cancer treated with chemoradiotherapy and celecoxib: a quantitative immunohistochemical analysis of RTOG C0128.

PURPOSE: This study aimed to measure expression of cyclooxygenase-2 (COX-2) and CD34 in pretreatment tumor biopsies from patients on the RTOG C0128 phase II study, and to correlate expression of these biomarkers, using quantitative immunohistochemistry, with clinical outcome parameters. METHODS AND MATERIALS: Pretreatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative immunohistochemistry (AQUA®). Cox regression models and Fisher's exact test were used to explore associations between expression of the biomarkers and clinical end points. RESULTS: Eighty-four patients were accrued between 2001 and 2004; 78 were eligible and analyzable. Pathology specimen submission was optional; COX-2 expression was determined for 37 (47%) of patients, and CD34 scoring was determined for 34 (44%) of patients. Median follow-up was 44.5 months. In tumors where COX-2 data were available, 6 (16%) of 37 patients had local-regional failure; 4 of these patients had tumors with COX-2 scores below the AQUA® score median (hazard ratio, 0.39; 95% confidence interval, 0.07-2.16; P = 0.28). Of the 8 patients with disease-free survival failures, 5 had tumors with COX-2 levels below the median (hazard ratio, 0.49; 95% confidence interval, 0.12-2.04; P = 0.32). The 4 patients who died all had COX-2 levels below the median value. COX-2 levels below the median were associated with worse 2-year survival (Fisher's P = 0.046). There was no statistically significant association between CD34 status and clinical outcome. CONCLUSIONS: Low COX-2 expression measured by AQUA® was associated with worse overall survival in this subset of patients available for analysis from RTOG C0128. Application of AQUA® technology, in a larger study, will be required to definitively evaluate the association COX-2 with clinical outcome in cervical cancer.

Are the Choosing Wisely Canada Cancer recommendations relevant and up to date with the current evidence?

INTRODUCTION: The Choosing Wisely (CW) Canada campaign was launched in 2012 to identify low-value, unnecessary and/or harmful services that are frequently used. The CW Canada Cancer list was developed in 2014 by a task force convened by the Canadian Partnership Against Cancer. The list outlines ten harmful or low-value practices that oncologists should avoid. We conducted a study of oncologists to understand the familiarity with the current recommendations and whether these continue to be relevant and up to date. METHODS: An electronic survey was developed by the members of the CW Oncology Working Group and distributed to practicing oncologists. The survey consisted of questions on 1) the familiarity of the existing CW Canada Cancer list 2) the relevance of the current list to current evidence and 3) any recommendation(s) that could be added or removed from the existing list. Descriptive statistics were used to analyze responses and narrative analysis was used to identify themes in open-ended questions. RESULTS: Between January 14 and May 3, 2022, 151 survey responses were received (overall response rate of 20 %) from 68 medical oncologists (45 % of study cohort, response rate 32 %), 54 radiation oncologists (36 % of study cohort, response rate 14 %) and 29 surgical oncologists (19 % of study cohort, response rate 18 %). Seventy-nine percent (120/151) of respondents were familiar with the current list and 65 % (78/119) said they implemented the recommendations "always" or "most of the time". Eight recommendations had > 80 % agreement that they were relevant and up to date with current evidence. There was interest in adding a new recommendation to avoid whole brain radiation and consider stereotactic radiosurgery (SRS) in patients with ≤ 4 brain metastases. CONCLUSIONS: There is excellent familiarity with the CW Canada Cancer list amongst the survey respondents and most recommendations continue to be relevant and up to date with current evidence. There is an opportunity to educate physicians about the intent of the campaign and to add a new recommendation on the use of SRS for patients with a limited number of brain metastases. There is also an opportunity to identify barriers at the patient, provider and institution level that are hindering adoption of the CW Canada Cancer list POLICY SUMMARY: This survey will impact implementation and publication of an updated CW Canada Cancer list.

The Choosing Wisely Oncology Canada Cancer List: An Update.

BACKGROUND: Choosing Wisely (CW) Canada is a national campaign to identify unnecessary or harmful services that are frequently used in Canada. The original CW Oncology Canada Cancer list was developed in 2014. A CW Oncology Canada working group was established to review new evidence and guidelines and to update the current CW Oncology Canada Cancer List. METHODS: Between January and March 2022, we conducted a survey of members of the Canadian Association of Medical Oncology (CAMO), Canadian Association of Radiation Oncology (CARO) and the Canadian Society of Surgical Oncology (CSSO). We took the feedback from the survey, including potential new recommendations as well as those that were thought to be no longer relevant and up to date, and conducted a literature review with the assistance of the Canadian Agency for Drugs and Technology in Health (CADTH). The final updated list of recommendations was made by the CW Oncology Canada working group based on a consensus process. RESULTS: We reviewed two potential recommendations to add and two potential recommendations to remove from the existing CW Oncology Canada Cancer List. The recommendation "Do not prescribe whole brain radiation over stereotactic radiosurgery for patient with limited brain metastases (≤4 lesions)" was supported by several evidence-based guidelines with the strength of recommendations ranging from strong to moderate and the quality of evidence ranging from level 1 to level 3. After reviewing the evidence, the working group felt that the other potential recommendation to add and the two potential recommendations to remove did not have sufficient strength and quality of evidence at this time to be added or removed from the list. CONCLUSION: The updated Choosing Wisely Oncology Canada Cancer List consists of 11 items that oncologists should question in the treatment of patients with cancer. This list can be used to design specific interventions to reduce low value care.

Long-Term Patient-Reported Quality of Life of Anal Cancer Survivors Treated With Intensity Modulated Radiation Therapy and Concurrent Chemotherapy: Results From a Prospective Phase II Trial.

PURPOSE: Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. METHODS AND MATERIALS: Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. RESULTS: For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months. CONCLUSIONS: Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

Changing Landscape of Radiation Therapy for Advanced Cervical Cancer With a Focus on Interstitial Brachytherapy: A Canadian Practice Patterns Survey.

PURPOSE: To document the evolution of radical radiation therapy and interstitial brachytherapy (ISBT) utilization practice patterns across Canada, including use of imaging, technical details, and usage of anesthesia/analgesia, and to compare advanced (AC) versus nonadvanced (nAC) brachytherapy (BT) center practices. METHODS AND MATERIALS: All Canadian centers with BT services were identified. One gynecology radiation oncologist per center was sent a 64-item questionnaire regarding the center's practice for patients with cervical cancer. Centers were categorized based on availability of advanced BT expertise (AC) versus those referring patients to other centers for advanced BT techniques (nAC). Aggregate responses are reported and compared with practice patterns identified in our previous survey. Descriptive statistics were used to summarize data, and the Fisher exact test, Fisher-Freeman-Halton, or Mann-Whitney-Wilcox test was used for comparisons. RESULTS: Thirty-seven of 38 respondents completed the survey (response rate: 97.4%). Compared with 2015, there has been an increase in utilization of magnetic resonance imaging as the sole imaging modality for BT planning: 3 of 26 (11%) versus 12 of 37 (32%; P = .03). The number of centers with the ability to perform ISBT increased in 2020 compared with 2015 (26/37 [70%] vs 13/26 [50%], P = .710); this trend is likely due to an increase in use of hybrid (Vienna, Utrecht, Venezia) applicators (36% [2015] vs 84% [2020]; P = .175). Fifteen (40%) centers had the ability to perform perineal-ISBT (P-ISBT). Sixteen and 21 centers were identified as AC and nAC, respectively. All 16 AC centers had the ability to perform ISBT, compared with only 10 nAC centers (P < .001). A higher proportion of AC centers had fellowship-trained radiation oncologists performing brachytherapy, compared with nAC centers (94% vs 14%, P < .001). In terms of anesthesia, conscious sedation was the only available choice at low-patient-volume centers (8/37, 21%) performing intracavitary BT only. Those performing ISBT had choice of general, spinal, and epidural anesthesia. CONCLUSIONS: In Canada, high-quality, modern management radiation therapy practices are consistently offered to patients with cervical cancer. There is a trend toward increased utilization of ISBT. Accumulation of evidence toward the use of ISBT, increased utilization of high-quality imaging modalities such as magnetic resonance imaging, and availability of hybrid applicators are potential contributors for this upward trend.

Representation of Women in Canadian Radiation Oncology Trainees and Radiation Oncologists: Progress or Regress?

Purpose: The study objective was to determine the representation of women in Canadian radiation oncology (RO) trainees and the radiation oncologist workforce over time. Methods and Materials: Gender data for Canadian RO trainees (residents and fellows) and radiation oncologists were collected from the Canadian Post-MD Education Registry (1994-2021) and Canadian Medical Association (1994-2019). Visa trainees were excluded. Gender parity was defined as a 1:1 female-to-male ratio. Descriptive statistics were used to summarize the data. Results: Female trainee proportions varied with 2 rising trend periods (1994-1998: 38%-43%, P = .93; 2002-2014: 35%-51%, P = .53) and 2 regression trend periods (1998-2002: 43%-35%, P = .83; 2014-2021: 52%-35%, P = .011). Gender parity was observed in RO trainees between 2012 and 2016. The annual number of RO trainees ranged from 66 to 173 with 2 near-parallel periods of gender-associated growth (1994-1996; 2002-2008) and regression (1997-2001; 2009-2016) followed by gender divergence (2017-2021) with increasing male and decreasing female trainees. Nearly all Canadian regions, except Ontario, reached 50% or higher female representation in RO trainees during the study period. In the radiation oncologist workforce, female representation increased from 20% (54/271) to 37% (217/582) between 1994 and 2019, and all regions and age groups demonstrated higher female representation over time. Within radiation oncologist subgroups, age <35 years old and Quebec region cohorts reached gender parity. Conclusions: Representation of women varied in Canadian RO trainees and has fallen since 2014, whereas female representation generally increased in the radiation oncologist workforce over time. Gender parity was observed in RO trainees, radiation oncologists <35 years old, and radiation oncologists in Quebec. Recent declining female representation among RO trainees is worrisome, and further study is warranted to identify potential gender-based barriers in attracting women to the specialty.

Impact of the COVID-19 Pandemic on Canadian Radiation Oncology Practices.

PURPOSE: To survey Canadian radiation oncology (RO) practice leaders to determine the effect of the COVID-19 pandemic on radiation services and patient and staff issues in the early phase of the pandemic and 1 year later. METHODS AND MATERIALS: The RO leader (department or division head) from every Canadian cancer center with radiation services was identified. Two surveys were circulated to the identified leader via email from the Canadian Association of Radiation Oncology central office, using the SurveyMonkey survey tool: the first closed in June 2020 and the second (expanded) survey in June 2021, representing 2 points in time of the COVID-19 pandemic. Questions included patient volume, service interruptions and delays, and changes in scheduling and telemedicine use. Additional questions were included in the follow-up survey to determine further effects on disease presentation, volume, vaccination and access, and personnel issues. RESULTS: Telemedicine was widely adopted early in the pandemic and continued to be a common technique to communicate and connect with patients. Although many centers were deferring or delaying certain disease sites early in the pandemic, this was not as prevalent 1 year later. Reduced cancer screening and patients presenting with more advanced disease were concerns documented in the 2021 survey. A high level of concern regarding stress among health care professionals was identified. CONCLUSIONS: Canadian RO centers have faced numerous challenges during the COVID-19 pandemic but continued to provide timely and essential cancer care for patients with cancer. Future evaluation of RO center practices will be important to continue to document and address the effect of the COVID-19 pandemic on issues relevant to RO leaders, patients, and staff.