Omission of radiation therapy post breast conserving surgery.

Radiation therapy (RT) after breast conserving surgery decreases the risks of local recurrence and breast cancer mortality in the multidisciplinary management of patients with breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of post-operative RT in individual patients varies substantially. Clinical trials aiming to identify patients with low-risk early breast cancer in whom post-operative RT may be safely omitted, based on conventional clinical-pathologic variables alone, have not provided sufficiently tailored information on local recurrence risk assessment to guide treatment decisions. The majority of patients with early breast cancer continue to be routinely treated with RT after breast conserving surgery. This approach may represent over-treatment for a substantial proportion of the patients. The clinical impact of genomic signatures on local therapy decisions for early breast cancer has been remarkably modest due to the lack of high-level evidence supporting their clinical validity for assessment of the risk of local recurrence. Efforts to personalise breast cancer care must be supported by high level evidence to enable balanced, informed treatment decisions. These considerations underpin the importance of ongoing biomarker-directed clinical trials to generate the high-level evidence necessary for setting the future standard of care in personalised local therapy for patients with early breast cancer.

Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study.

BACKGROUND: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. METHODS: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). FINDINGS: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. INTERPRETATION: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. FUNDING: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

Harnessing Real-World Evidence to Advance Cancer Research.

Randomized controlled trials (RCTs) form a cornerstone of oncology research by generating evidence about the efficacy of therapies in selected patient populations. However, their implementation is often resource- and cost-intensive, and their generalisability to patients treated in routine practice may be limited. Real-world evidence leverages data collected about patients receiving clinical care in routine practice outside of clinical trial settings and provides opportunities to identify and address gaps in clinical trial evidence. This review outlines the strengths and limitations of real-world and RCT evidence and proposes a framework for the complementary use of the two bodies of evidence to advance cancer research. There are challenges to the implementation of real-world research in oncology, including heterogeneity of data sources, timely access to high-quality data, and concerns about the quality of methods leveraging real-world data, particularly causal inference. Improved understanding of the strengths and limitations of real-world data and ongoing efforts to optimise the conduct of real-world evidence research will improve its reliability, understanding and acceptance, and enable the full potential of real-world evidence to be realised in oncology practice.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Imaging Modalities for Early Detection of Pancreatic Cancer: Current State and Future Research Opportunities.

Pancreatic cancer, one of the most lethal malignancies, is increasing in incidence. While survival rates for many cancers have improved dramatically over the last 20 years, people with pancreatic cancer have persistently poor outcomes. Potential cure for pancreatic cancer involves surgical resection and adjuvant therapy. However, approximately 85% of patients diagnosed with pancreatic cancer are not suitable for potentially curative therapy due to locally advanced or metastatic disease stage. Because of this stark survival contrast, any improvement in early detection would likely significantly improve survival of patients with pancreatic cancer through earlier intervention. This comprehensive scoping review describes the current evidence on groups at high risk for developing pancreatic cancer, including individuals with inherited predisposition, pancreatic cystic lesions, diabetes, and pancreatitis. We review the current roles of imaging modalities focusing on early detection of pancreatic cancer. Additionally, we propose the use of advanced imaging modalities to identify early, potentially curable pancreatic cancer in high-risk cohorts. We discuss innovative imaging techniques for early detection of pancreatic cancer, but its widespread application requires further investigation and potentially a combination with other non-invasive biomarkers.

Breast Irradiation in Ductal Carcinoma In Situ.

There is strong and consistent evidence that whole breast irradiation after breast conserving surgery significantly decreases the risk of ipsilateral breast events, in situ or invasive, underpinning its established role in patients with ductal carcinoma in situ (DCIS). Pending publication of the full results of BIG 3-07/TROG 07.01 randomised trial, addition of tumour bed boost to whole breast irradiation is recommended in the presence of adverse clinical-pathologic features, and the use of moderately hypofractionated whole breast dose-fractionation schedules is supported. As published data supporting the use of adjuvant partial breast irradiation in patients with low-risk DCIS are limited, its off-study application should be limited to low-risk patients defined by international and national guidelines. Finally, low-risk patients may not derive clinically meaningful benefits from radiation therapy and research on molecular profiling is ongoing to improve prognostic precision and guide safe omission of radiation therapy after breast conserving surgery.

Factors involved in treatment decision making for women diagnosed with ductal carcinoma in situ: A qualitative study.

Whilst some of the diversity in management of women with ductal carcinoma in situ (DCIS) may be explained by tumour characteristics, the role of patient preference and the factors underlying those preferences have been less frequently examined. We have used a descriptive qualitative study to explore treatment decisions for a group of Australian women diagnosed with DCIS through mammographic screening. Semi-structured telephone interviews were performed with 16 women diagnosed with DCIS between January 2012 and December 2018, recruited through the LifePool dataset (a subset of BreastScreen participants who have agreed to participate in research). Content analysis using deductive coding identified three themes: participants did not have a clear understanding of their diagnosis or prognosis; reported involvement in decision making about management varied; specific factors including the psychosexual impact of mastectomy and perceptions of radiotherapy, could act as barriers or facilitators to specific decisions about treatment. The treatment the women received was not simply determined by the characteristics of their disease. Interaction with the managing clinician was pivotal, however many other factors played a part in individual decisions. Recognising that decisions are not purely a function of disease characteristics is important for both women with DCIS and the clinicians who care for them.

Postmastectomy radiotherapy: a review.

PURPOSE OF REVIEW: We review the role of postmastectomy radiotherapy (PMRT) in the management of patients with early breast cancer. RECENT FINDINGS: PMRT in patients with 4 or more involved axillary lymph nodes is the current standard of care but the indications for PMRT in patients with 1-3 involved nodes remain controversial. The Early Breast Cancer Trialists' Collaborative Group meta-analysis of randomised trials of PMRT provides the most comprehensive level 1 evidence base. However, its applicability in contemporary practice in the context of recent multidisciplinary advances in surgery, radiation therapy and systemic therapy remains challenging. SUMMARY: The lack of consensus on the indications for PMRT in patients with 1-3 positive nodes underpins the variations in the national and international guidelines on PMRT. We emphasise the need for contemporary randomised trial data, and the potential to refine patient selection for PMRT using novel biomarkers of recurrence and radiosensitivity.

Axillary dissection in sentinel lymph node positive breast cancer: Is the staging information worthwhile for patients?

AIMS: The Z0011 randomized trial demonstrated no significant difference in axillary recurrence rate or survival with or without axillary dissection in patients with a positive sentinel node biopsy. However, there is continuing controversy regarding the generalizability of its results, and axillary dissection provides additional pathologic staging information that may guide adjuvant therapy. Thus, axillary dissection after positive sentinel node biopsy is being further investigated in an actively recruiting randomized trial. We elicited patients' preferences for axillary dissection versus no axillary dissection after positive sentinel node biopsy for early breast cancer. METHODS: Patients who had undergone axillary dissection after positive sentinel node biopsy as part of breast conserving therapy were provided with a validated, self-rated questionnaire. The questionnaire comprised two trade-off questions to determine the maximum chance of developing arm side-effects from axillary dissection to justify the benefit of additional axillary staging information. Social, demographic, and clinical details were collected. RESULTS: Ninety-nine of the 126 eligible patients returned the questionnaire and 76 completed the trade-off assessment. The median age of participants was 62 years. The median numbers of sentinel and axillary nodes removed were 2 and 12, respectively. Forty-seven percent of participants had arm swelling or tenderness of any severity. Seventy-five percent of participants would have axillary dissection even if the chance of arm side-effects like they had experienced was 100%. CONCLUSION: Most patients with early breast cancer preferred axillary dissection after positive sentinel node biopsy for the additional staging information even though there was no survival benefit from axillary dissection.

Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial.

BACKGROUND: BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years. METHODS: The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov, NCT00470236. FINDINGS: Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05-0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06-0·20; p=0·00021), persisting at 24 months (0·13 [0·06-0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03-0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [-0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference -1·10 [95% CI -1·79 to -0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy. INTERPRETATION: Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending. FUNDING: National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast.

PURPOSE: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. RESULTS: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). CONCLUSIONS: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial.

BACKGROUND: Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. METHODS: We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. FINDINGS: Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). INTERPRETATION: External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. FUNDING: Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

Individualised target volume selection and dose prescription after conservative surgery, mastectomy and reconstruction.

Progress in radiotherapy (RT) for early breast cancer, driven by advances in radiobiology and radiation techniques is enabling individualised target volume and dose-fractionation according to recurrence risk. Conventionally fractionated WBI (CF-WBI) has been justified on the basis that it spares dose-limiting late-responding normal tissues more than breast cancer. However, randomised clinical trials (RCTs) testing hypofractionated WBI (HF-WBI) showed equivalent tumour control, improved acute toxicity and similar late toxicity between selected HF-WBI schedules and CF-WBI. RCTs showed that tumour bed boost (TBB) after WBI improved local control but increased breast fibrosis compared to no TBB. RCT comparing sequential TBB and simultaneous integrated TBB using dose intensity modulation showed similar toxicity. Partial breast irradiation (PBI) limits target volume to the tumour bed, which permits safe treatment acceleration. RCTs showed that PBI resulted in low local relapse rates but in some RCTs, higher rates of late toxicity and adverse cosmetic outcome than WBI. Given heterogeneity of PBI techniques, target volumes and dose-fractionation schedules used in RCTs, interpretation of results to distinguish whether outcome variations are caused by target volume or dose-fractionation effect is challenging. RCTs demonstrating efficacy of post-mastectomy RT (PMRT) included the chest wall and regional nodes but did not distinguish relative contributions of nodal target sub-volumes. In patients with smaller axillary tumour burden, IMC irradiation is controversial. RCTs were not powered for comparison between CF-PMRT and HF-PMRT. No increase in arm or shoulder dysfunction with HF-PMRT was observed. No RCT data exist on HF-PMRT in patients with breast reconstruction.

Implementation of a Multidisciplinary Model of Care for Women With Metastatic Breast Cancer: Challenges and Lessons Learned.

INTRODUCTION: The present study examined the feasibility and effects of integrating a multidisciplinary team (MDT) model of care for women with metastatic breast cancer (MBC) into a large Australian cancer center. The challenges encountered and lessons learned are described. PATIENTS AND METHODS: In the present prospective, longitudinal, mixed-methods implementation study, the MDT model included face-to-face consultations with a breast care nurse and social worker, followed by a MDT case discussion and face-to-face delivery of a personalized management plan. Data were collected to describe the cohort of women living with MBC who had attended a specialist breast cancer service and their supportive care needs. RESULTS: A total of 62 women with median age of 60 years (interquartile range [IQR], 37-82 years) participated. The median interval from the first breast cancer diagnosis was 5.7 years (IQR, 2.0-11.6 years), and the median interval from the diagnosis of MBC was 2.0 years (IQR, 0.9-3.6 years). The MDT care model required new resources and cross-sector participation. However, the participants indicated a preference for personalized needs assessment and care planning at the diagnosis of MBC. CONCLUSIONS: The results highlight the challenges of implementing and evaluating an MDT care model for women with MBC. The model coordinated MDT collaboration to strengthen the delivery of complex care plans. Investment in cross-sector partnerships to optimize care coordination for women with MBC was needed.

Patient-reported outcomes in ductal carcinoma in situ: A systematic review.

Ductal carcinoma in situ (DCIS) is a pre-invasive breast cancer with excellent prognosis but with potential adverse impacts of diagnosis and treatment on quality of life and other patient-reported outcomes (PROs). We undertook a systematic review to synthesise current evidence about PROs following diagnosis and treatment for DCIS. We searched five electronic databases (from database inception to November 2015), cross-referenced and contacted experts to identify studies that reported PROs after DCIS treatment. Two reviewers independently applied inclusion and quality criteria, and extracted findings. Of 2130 papers screened, 23 were eligible, reporting 17 studies. Short- and long-term PRO evidence about differences between DCIS treatment options was lacking. Evidence pooled across treatments indicated core aspects of quality of life (physical, role, social, emotional function, pain, fatigue) and psychological distress (anxiety, depression) were impacted significantly initially, with most aspects returning to population norms by 6-12 months, and all by 2 years post-operatively. Fears of recurrence and dying from breast cancer were exaggerated, occurred early and persisted for many years. Sexuality and body image impacts were generally low and resolved within 1-3 months after surgery. A minority of women experienced considerable impact, including depression and sexual issues associated with body image problems. Well-powered PRO studies are required to track recovery trajectories and long-term impacts of the range of contemporary and emerging local and systemic treatments for DCIS. PRO data would enable care providers to prepare patients for short-term sequelae and enable patients who have treatment options to exercise preferences in choosing among them.

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.).