Accelerated Partial Breast Irradiation Using 5 Daily Fractions: A Prospective, Phase 2, Multicenter Trial of Cosmetic Outcomes and Toxicity-ACCEL Final Results.

PURPOSE: This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI). METHODS AND MATERIALS: The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI. The primary endpoint was noninferiority of 2-year cosmesis using the RAPID trial's WBI arm as the control arm. A global consensus cosmetic score using a European Organisation for Research and Treatment of Cancer rating scale score of excellent, good, fair, or poor for each patient at baseline and 2 years was generated by a panel of 5 radiation oncologists using photographs of treated and untreated breasts. RESULTS: From 2016 to 2019, 298 eligible women were enrolled. By the 2-year follow-up, 76 patients had been lost or withdrawn and 3 had died, resulting in 219 patients available for complete, 2-year photographic cosmetic evaluation. The median follow-up for all participants was 4.7 years (IQR, 3.8-5.5 years). No patient had a fair or poor cosmetic score at the 2-year evaluation. Cosmesis was better or unchanged for 97% of patients and worse for 3% (excellent to good), and no cosmetic failures occurred. The confidence intervals were 0.88 (0.86-0.90) and 1.00 (0.99-1.00) for the RAPID and ACCEL trials, respectively. CONCLUSIONS: Cosmetic degradation with 5 daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial.

The transition in practice to reduce bolus use in post-mastectomy radiotherapy: A dosimetric study of skin and subcutaneous tissue.

To inform clinical practice for women receiving post-mastectomy radiotherapy (PMRT), this study demonstrates the dosimetric impact of removing daily bolus on skin and subcutaneous tissue. Two planning strategies were used: clinical field-based (n = 30) and volume-based planning (n = 10). The clinical field-based plans were created with bolus and recalculated without bolus for comparison. The volume-based plans were created with bolus to ensure a minimum target coverage of the chest wall PTV and recalculated without bolus. In each scenario, the dose to superficial structures, including skin (3 mm and 5 mm) and subcutaneous tissue (a 2 mm layer, 3 mm deep from surface) were reported. Additionally, the difference in the clinically evaluated dosimetry to skin and subcutaneous tissue in volume-based plans were recalculated using Acuros (AXB) and compared to the Anisotropic Analytical Algorithm (AAA) algorithm. For all treatment planning strategies, chest wall coverage (V90%) was maintained. As expected, superficial structures demonstrate significant loss in coverage. The largest difference observed in the most superficial 3 mm where V90% coverage is reduced from a mean (± standard deviation) of 95.1% (± 2.8) to 18.9% (± 5.6) for clinical field-based treatments with and without bolus, respectively. For volume-based planning, the subcutaneous tissue maintains a V90% of 90.5% (± 7.0) compared to the clinical field-based planning coverage of 84.4% (± 8.0). In all skin and subcutaneous tissue, the AAA algorithm underestimates the volume of the 90% isodose. Removing bolus results in minimal dosimetric differences in the chest wall and significantly lower skin dose while dose to the subcutaneous tissue is maintained. Unless the skin has disease involvement, the most superficial 3 mm is not considered part of the target volume. The continued use of the AAA algorithm is supported for the PMRT setting.

Has Radiotherapy Been Successfully Implemented in Alberta's Small Cities? A Review of Alberta's Regional Cancer Centre Network from 2010-2020.

The expansion of cancer services closer to home has become a major focus of publicly funded healthcare, with cancer organizations attempting to invest in smaller centers by integrating radiotherapy into these facilities. In Canada this has resulted in Ontario, British Columbia and Alberta investing in 12 expanded regional centers over the past 20 years. Quebec, Manitoba and Nova Scotia have made similar investments. Alberta's three new centers opened in 2010, 2013 and 2021 (projected). This study examined improvements in wait times and patient throughput between 2010 and 2020, and highlighted strategies that will support the sustainability and growth of clinical activity through to 2030. Significant improvement in ready to treat wait times for radiotherapy have resulted from opening two centers, and the provincial throughput for patients requiring systemic or radiotherapy has gone up by 16%. A patient satisfaction survey demonstrated that rural patients are happy with their care and desire the provision of more of their cancer treatment closer to home. An expert panel provided recommendations on what needs to be done to stabilize recruitment and retention.

A retrospective analysis to demonstrate achievable dosimetry for the left anterior descending artery in left-sided breast cancer patients treated with radiotherapy.

PURPOSE: To demonstrate achievable dose for the left anterior descending artery (LAD) for left-sided breast cancer patients. METHODS: A retrospective analysis was conducted on all left-sided breast cancer patients receiving whole breast or post-mastectomy chest wall irradiation between 2013 and 2018. All patients in this study were treated with tangent-based techniques with the LAD prospectively contoured as routine clinical care. This large patient cohort was used to benchmark achievable mean doses to the LAD in the context of heart dose. The primary cohort of study were patients undergoing treatment with deep-inspiration breath-hold (DIBH), stratified by internal mammary nodes (IMN) inclusion. In all cases, the median (25th-75th percentile) is reported. RESULTS: A total of 1221 left-sided breast cancer patients were included in this study with 1045 in the DIBH cohort. The median heart mean dose for this cohort is 1.0 Gy (0.8-1.1). For patients treated in DIBH with IMNs included (n = 422), the median of the mean LAD dose is 3.6 Gy (2.9-4.4) and, for patients treated in DIBH with IMNs excluded (n = 623), the median of the mean LAD dose is 3.2 Gy (2.5-3.8). CONCLUSIONS: Appropriate respiratory management can be utilized to achieve low dose to the LAD for the majority of patients without compromising target coverage.

Results of the ACCEL trial: Dosimetry in accelerated partial breast irradiation.

PURPOSE: To report the achieved dosimetry in the ACCEL trial and compare the results to reported dosimetry from the major accelerated partial breast irradiation (APBI) phase III trials. METHODS: The ACCEL trial was a single arm, phase II, prospective cohort study. A five-field, inverse-planned, IMRT strategy was employed using a class solution technique to increase planning consistency including high dose conformity and low normal tissue dose to the ipsilateral breast. RESULTS: Between 2016 and 2019, 283 patients were treated with 27 Gy in five fractions in consecutive days. The average PTV conformity index was 1.1. For the ipsilateral breast, the median (range) volume receiving 95% and 50% of the prescription dose was 9.7% (3.2-22.4) and 30.3% (11.1-54.6), respectively. Compared to major APBI phase III trial constraints, this reduction in irradiated volume at the 95% and 50% isodose levels represents a reduction of 209 cm3 and 265 cm3, respectively. CONCLUSION: The IMRT planning strategy employed in the ACCEL trial demonstrated consistent and superior dosimetry by comparison to conventionally used 3D CRT techniques. Future APBI trials should update dosimetric constraints.

The Role of Coaches within Academic Medical Departments: Is There Value to Integrating This into Academic Mentorship Programs?

This study evaluated the benefits of formal coaching within a mentorship program in a Canadian academic medical department. Between April 2016 and September 2018, an executive coach was made available to members of the Department of Oncology at the University of Calgary. Thirty-seven individuals sought and received formal coaching during this period, using up an average of four hourly sessions; of these individuals, 13% (20/150) are full-time faculty. Issues that facilitated interest in coaching included the following: needing to develop an individual life plan, wanting to improve work-life balance/time management and seeking advice about promotion or job application. This study found that coaching enabled participants to address their concerns 70% of the time and describes the elements of a coaching function within academic medical departments. We strongly recommend that academic departments provide opportunities for interested individual academics to receive coaching.

A Framework for Clinical Validation of Automatic Contour Propagation: Standardizing Geometric and Dosimetric Evaluation.

PURPOSE: The objective of this work was to outline and demonstrate a standardized framework for evaluating automatically propagated contour quality against expert contours. A 2-pronged approach is used to evaluate contour quality: a geometric evaluation to identify geometric and spatial discrepancies between propagated and expert contours, and a comprehensive dosimetric comparison to provide clinical context for the results. METHODS AND MATERIALS: The standardized framework requires a primary image, with reference contours and a radiation therapy treatment plan, and a secondary image. Reference contours are automatically propagated onto the secondary image anatomy and compared with expert contours obtained in an interobserver study. The standardized framework outlines geometric and dosimetric evaluation methodologies for determining indistinguishability between propagated and expert contours in a cohort analysis. Propagated contours are geometrically compared with expert contours in terms of the Dice similarity coefficient and the mean distance to agreement. Statistical analysis is performed on the central tendency and variability of Dice similarity coefficient and mean distance to agreement values over the patient cohort. Dosimetric evaluation involves computing the mean and 95% confidence intervals for the differences in cumulative dose-volume histograms for propagated and expert contours. A case study in accelerated partial breast irradiation was shown to demonstrate the framework. RESULTS: The standardized framework was applied to a case study of 24 patient data sets with 3 radiation oncologists providing the expert contours. Cohort analysis indicated that propagated contours were geometrically indistinguishable and dosimetrically distinguishable from expert contours. CONCLUSIONS: The recommended framework standardizes the comparison of geometric and dosimetric parameters to demonstrate indistinguishability of propagated contours from expert contours. Adoption of this framework is vital for consistent and comprehensive validation of automatic contour propagation for use in large-scale cohort analyses.

Patient-Reported Satisfaction Following Radiation of Implant-Based Breast Reconstruction.

BACKGROUND: Little is known with regard to patient-reported outcomes (PROs) in the setting of implant-based reconstruction (IBR) with post-mastectomy radiation therapy (PMRT). METHODS: We identified patients who underwent immediate IBR from a prospectively compiled database. The Breast Reconstruction Satisfaction Questionnaire (BRECON-31) was scored and compared between patients with and without PMRT. RESULTS: Sixty-four women met the study criteria. Forty-eight did not receive PMRT and 16 did. Nine women had an unanticipated indication for PMRT. The PMRT group was similar to the control group with regard to baseline characteristics (ie, age, marital status, body mass index, tobacco use, and comorbidities). However, treatment and oncologic characteristics (eg, diagnosis, tumour characteristics, systemic therapy use) differed. Of all complications, only capsular contracture rates differed (1.2% vs 13%; P = .01). Of the 9 subscales, 7 showed no difference in satisfaction between the groups. Radiated women scored lower in the arm concerns and breast appearance subscales. Scores were similar whether the indication for PMRT had been anticipated or not. DISCUSSION: Women with immediate IBR scored similarly to their nonradiated counterparts across 7 of 9 domains of satisfaction. Arm concerns and breast appearance scores are lower with PMRT, likely secondarily to more extensive nodal procedures in higher stage patients and to the side effect profile of radiotherapy. Our findings are in line with the few available studies using other PRO tools to evaluate the impact of PMRT on patient satisfaction and studies objectively measuring the effect of PMRT on arm morbidity and cosmetic outcomes.

HISTORIQUE: On ne sait pas grand-chose de ce que les patientes pensent des résultats (PPR) de leur reconstruction par implant (RPI) lorsqu'elles subissent une radiothérapie après leur mastectomie (RTAM). MÉTHODOLOGIE: Les chercheurs ont recensé les patientes qui ont subi une RPI à partir d'une base de données compilée rétrospectivement. Ils ont calculé le score du questionnaire de satisfaction sur la reconstruction mammaire (BRECON-31) et l'ont comparé entre les patientes avec ou sans RTAM. RÉSULTATS: Soixante-quatre femmes respectaient les critères d'étude. Quarante-huit n'ont pas subi de RTAM et 16 en ont subi une. Neuf femmes ont reçu une indication non anticipée de RTAM. Le groupe ayant subi la RTAM était semblable au groupe témoin pour ce qui est des caractéristiques de base (âge, état matrimonial, indice de masse corporelle, tabagisme et comorbidités). Cependant, les caractéristiques thérapeutiques et oncologiques (diagnostics, caractéristiques de la tumeur, utilisation systémique de traitements) étaient différentes. De toutes les complications, seuls les taux de contracture capsulaire étaient différents (1,2 par rapport à 13 %, P = 0,001). Des neuf sous-échelles, sept ne révélaient pas de différence en matière de satisfaction entre les groupes. Les femmes ayant subi une radiothérapie obtenaient un score plus bas pour ce qui est des sous-échelles d'inquiétudes relatives au bras et à l'apparence des seins. Les scores étaient semblables, que l'indication de RTAM ait été anticipée ou non. EXPOSÉ: Les femmes qui avaient subi une RPI ont obtenu un score semblable à celui de leurs homologues qui n'en avaient pas subi dans sept des neuf domaines de satisfaction. Le score d'inquiétude relatif au bras et le score d'apparence du sein sont plus faibles en cas de RTAM, probablement à cause d'interventions nodales plus radicales chez des patientes à un stade plus avancé et du profil d'effets secondaires de la radiothérapie. Les constatations des chercheurs correspondent à celles des quelques études faisant appel à d'autres outils de PPR pour évaluer les répercussions de la RTAM sur la satisfaction des patientes et les études qui mesurent objectivement l'effet de la RTAM sur la morbidité du bras et les résultats esthétiques.

One-Year Cosmesis and Fibrosis From ACCEL: Accelerated Partial Breast Irradiation (APBI) Using 27 Gy in 5 Daily Fractions.

PURPOSE: To report 1-year cosmesis and toxicity outcomes of a prospective, phase II trial of accelerated partial breast irradiation using intensity-modulated radiation therapy (RT) to deliver 27 Gy in 5 daily fractions. METHODS AND MATERIALS: Node-negative breast cancer patients after breast conserving surgery with clear excision margins, with physician-assessed excellent or good baseline cosmesis were invited to participate in a prospective clinical trial to receive 27 Gy in 5 daily fractions to the expanded primary site. Clinical photographs and European Organisation for Research and Treatment of Cancer cosmetic score were collected at baseline prior to RT and 1-year after radiation therapy. A protocol-specified, interim analysis was scheduled when 50 patients had completed 1-year follow-up. A panel of 6 physicians provided a consensus global cosmetic score (termed panel-assessed score) based on clinical photographs at baseline and 1-year. Fibrosis and telangiectasia were prospectively assessed by clinical research staff at clinic visits. RESULTS: At the interim analysis, 55 patients had baseline and 1-year post-RT images available. Most patients had either an improvement (53%) or no change (40%) in cosmesis from baseline to 1-year. Among 49 patients with excellent or good panel-assessed score at baseline, only 2 (4%) patients had a fair score at 1-year post-RT, indicating cosmetic deterioration. No patients had evidence of telangiectasia or grade 2 or higher fibrosis. There were no recurrences. CONCLUSIONS: APBI using 27 Gy in 5 daily fractions achieved acceptable 1-year cosmesis and no grade 2 fibrosis. A preplanned stopping rule of 5% grade 2+ fibrosis was not observed. The trial will continue to the planned target accrual of 274 patients.

'Driving' Rates Down: A Population-Based Study of Opening New Radiation Therapy Centers on the Use of Mastectomy for Breast Cancer.

BACKGROUND: Two new cancer centers providing radiation therapy opened in Alberta, Canada, in 2010 and 2013, respectively. We aimed to assess whether opening the new RT centers influenced mastectomy rates for breast cancer. METHOD: Breast cancer patients who underwent surgery from 2004 through 2015 were identified from the Alberta Cancer Registry. Mastectomy rates for 64 predefined health status areas (HSAs) were calculated after adjusting for patient and system factors. Variations in mastectomy rates among the HSAs were quantified using weighted coefficient of variation (CV). Multivariable logistic regressions were performed to determine associations between driving time and mastectomy use in the entire cohort and in subgroups. RESULTS: Of the 21,872 patients, the proportion of patients who lived a ≤ 60 min drive from the nearest RT center significantly increased from 68.8% (95% CI 67.7-69.9%) to 80.7% (95% CI 79.5-81.9%) during the study period. Concurrently, the crude provincial mastectomy rate decreased from 56.2% (95% CI 55.3-57.1%) to 45.3% (95% CI 44.1-46.5%). However, variation in adjusted mastectomy rates (weighted CV) across the 64 HSAs increased from 9.5 to 14.6. Factors associated with mastectomy included age, larger tumor size, lymph node involvement, higher tumor grade, molecular subtype, lobular histology type, more comorbidities, academic institution, region, earlier period of diagnosis, and longer driving time to the nearest RT center. CONCLUSIONS: Opening new RT centers in previously underserved regions reduced driving times to the nearest center, and was associated with a reduction in mastectomy rates; however, these reductions among regions across the province were not uniform.

Barriers and enablers to academic health leadership.

Purpose This study sought to identify the barriers and enablers to leadership enactment in academic health-care settings. Design/methodology/approach Semi-structured interviews ( n = 77) with programme stakeholders (medical school trainees, university leaders, clinical leaders, medical scientists and directors external to the medical school) were conducted, and the responses content-analysed. Findings Both contextual and individual factors were identified as playing a role in affecting academic health leadership enactment that has an impact on programme development, success and maintenance. Contextual factors included sufficient resources allocated to the programme, opportunities for learners to practise leadership skills, a competent team around the leader once that person is in place, clear expectations for the leader and a culture that fosters open communication. Contextual barriers included highly bureaucratic structures, fear-of-failure and non-trusting cultures and inappropriate performance systems. Programmes were advised to select participants based on self-awareness, strong communication skills and an innovative thinking style. Filling specific knowledge and skill gaps, particularly for those not trained in medical school, was viewed as essential. Ineffective decision-making styles and tendencies to get involved in day-to-day activities were barriers to the development of academic health leaders. Originality/value Programmes designed to develop academic health-care leaders will be most effective if they develop leadership at all levels; ensure that the organisation's culture, structure and processes reinforce positive leadership practices; and recognise the critical role of teams in supporting its leaders.

Determining the need and utilization of radiotherapy in cancers of the breast, cervix, lung, prostate and rectum: A population level study.

PURPOSE: Determining the appropriate rate of radiotherapy (RT) utilization is important for health care planning and resource allocation. The difference between the observed and the appropriate RT rate is influenced by the choice of a criterion based benchmarking (CBB) or evidence-based estimates (EBEST) measure. Our primary objective was to determine the utilization of radiotherapy for cancers of the breast (B), cervix (C), lung (L), prostate (P) and rectum (R) in Alberta (AB) Canada and to compare the observed RT rates to estimates of need derived from the criterion based benchmarking (CBB) and evidence-based estimates (EBEST). MATERIALS AND METHODS: All incident cases of B,C,L,P and R cancers diagnosed in AB during 2004-8 (prior to the decentralization of provincial RT capacity) were identified from the Alberta Cancer Registry. Patients receiving RT within one year (RT-1y) of diagnosis were identified and the proportion receiving RT-1y was then calculated. Factors associated with RT utilization were analysed by region. Estimates of the need for RT were derived from CBB and EBEST methods in the literature. RESULTS: A total of n=68,164 cancer cases were identified from the ACR. RT-1y rates (95% C.I.) were B: 51.5% (50.1-52.9), C: 48.9% (43.8-54.0), L: 37.1% (35.4-38.8), P: 26.9% (25.1-28.7) and R: 39.3% (36.5-42.1). Observed rates of RT in AB were lower than estimates derived using the CBB and EBEST estimates. Shortfalls varied across cancer sites according to whether a CBB or EBEST estimate was used ranging from a low of -0.3% in cancer of the cervix to a high of 30.3% in rectal cancer. CONCLUSIONS: RT shortfalls exist in the utilization of RT in AB, Canada despite centralized cancer care and a publically funded health care system. Decisions to address shortfalls need to be mindful of how model selection can impact on findings.

Canadian Cancer Programs Are Struggling to Invest in Development of Future Leaders: Results of a Pan-Canadian Survey.

Cancer agencies within Canada operate with a variety of leadership models, assuming that future leaders are identified, developed and supported by institutions other than their own. A literature review, comprehensive survey and structured interviews were conducted to illuminate the perceptions of leadership in Canadian cancer centres. The major finding from the study is the significant gap between the competencies that leaders acknowledge as being important and the lack of development programs for future and current leaders. The study also showed there is agreement on preferred leadership models and the personal traits that identify future leaders worthy of development. Given the current struggles of leadership, the authors suggest that cancer agencies need to strategize how to advance succession planning and leadership development frameworks.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. METHODS: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. RESULTS: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). CONCLUSIONS: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.

PURPOSE: This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer. PATIENTS AND METHODS: Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability. RESULTS: PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms. CONCLUSION: TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.

Quality indicators for ductal carcinoma in situ (DCIS) of the breast: development using a multidisciplinary delphi process and its use in monitoring population-based treatment.

BACKGROUND AND OBJECTIVES: Evaluation of the management of DCIS poses challenges, as standard breast cancer outcome measures such as mortality do not apply. We have developed quality indicators (QIs) to measure the quality of DCIS treatment in Alberta, Canada. METHODS: A modified Delphi process was used to determine QIs in the treatment of DCIS after review of evidence-based clinical practice guidelines. Patients diagnosed with DCIS from 2000 to 2001 (cohort 1) and 2009-2010 (cohort 2) were identified from the Alberta Cancer Registry and QIs were retrospectively abstracted. RESULTS: The expert panel developed eight QIs to assess the overall quality of care for DCIS patients. Five hundred eighty eligible patients were identified in the two cohorts. There was significant improvement in radiation oncology referral, radiation post lumpectomy and complete pathology reporting. Axillary staging significantly increased from 20% (axillary dissection in cohort 1) to 60% (sentinel node biopsy in cohort 2). Other QIs did not differ significantly. CONCLUSIONS: By developing QIs, performance measures for DCIS may assessed and compared over time. Although there have been significant improvements with pathology reporting and radiation oncology assessment and treatment, axillary staging rates are unexpectedly high, necessitating further investigation.

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 significance of tumoral ERCC1 status in patients with locally advanced cervical cancer treated with chemoradiation therapy: a multicenter clinicopathologic analysis.

PURPOSE: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. METHODS AND MATERIALS: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. RESULTS: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). CONCLUSIONS: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.

Defining treatment for brain metastases patients: nihilism versus optimism.

AIMS: Treatment of brain metastases patients has included whole brain radiotherapy (WBRT) for over 50 years, and there is much data showing this to be associated with short-term gains. The integration of resection and radiosurgery to these patients allows some better prognostic groups to experience long-term local control and improvement in quality of life. The recursive partitioning analysis of the Radiation Therapy Oncology Group (RTOG) has been used as a predictive model for over a decade to identify three classes of patients. Number of lesions has been used to define treatment for a good prognostic subgroup that is eligible for surgery or radiosurgery, but there are few prospective studies of poorer prognosis brain metastases patients to evaluate the influence of number of lesions on the prediction of outcome. We examined patient, treatment and outcome parameters of all brain metastases patients in a 5-year period so that we could measure outcome and evaluate various factors on survival. METHODS AND RESULTS: This was a population-based study of all brain metastases patients in Southern Alberta between 2000 and 2005. It used an Excel spreadsheet database and STATA 8 software to analyze outcomes. The study included 568 patients representing 4.4% of our radiotherapy population. Median age, performance status and distribution of primary disease sites were comparable with other large series. Overall survival for the whole group was 3.05 months. Independent factors predicting for improved overall survival included younger age, KPS <70, less than four lesions and the use of stereotactic radiosurgery. Presence of extracranial disease or persistence of primary disease did not adversely impact survival outcome. CONCLUSIONS: This series shows that the number of lesions is a strong predictor of outcome. Integration of this factor into a decision-making model allows for identification of not only good prognosis patients who will benefit from aggressive treatment but it also facilitates decision making for poorer prognosis patients who are less likely to benefit from WBRT. Recursive partitioning RTOG class 2 and 3 patients with more than three lesions did particularly poor and had an overall survival of 3 months with WBRT. We question the value of WBRT in this subgroup and wonder if best supportive care would be more justifiable given the low survival figures achieved.

International brachytherapy practice patterns: a survey of the Gynecologic Cancer Intergroup (GCIG).

PURPOSE: To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm). METHODS AND MATERIALS: A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey. RESULTS: A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002). CONCLUSION: Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials.