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6. American College of Surgeons. Categories of Accreditation. Available at: http://www.facs.org/cancer/coc/categories.html. Accessed November 9, 2014. 7. Pierce LJ. The use of radiotherapy after mastectomy: a review of the literature. J Clin Oncol 2005;23:1706e1717. 8. Shirvani SM, Pan IW, Buchholz TA, et al. Impact of evidencebased clinical guidelines on the adoption of postmastectomy radiation in older women. Cancer 2011;117:4595e4605. 9. Yao K, Hou N, Winchester D, et al. Trends in postmastectomy radiation therapy for patients with T3 or N2 disease. Abstract presented at the 2012 Society of Surgical Oncology Annual Cancer Symposium, March 21 24, 2012, Orlando, FL. 10. Chu QD, Smith MH, Williams M, et al. Race/ethnicity has no effect on outcome for breast cancer patients treated at an academic center with a public hospital. Cancer Epidemiol Biomarkers Prev 2009;18:2157e2161. 11. Punglia RS, Hughes ME, Edge SB, et al. Factors associated with guideline-concordant use of radiotherapy after mastectomy in the national comprehensive cancer network. Int J Radiat Oncol Biol Phys 2008;72:1434e1440.
Discussion DR STEPHEN GROBMYER (Gainesville, FL): I have several comments and questions for the authors. The conclusions of the manuscript are predicated on the accuracy of the National Cancer Database (NCDB). Have there been any studies, as was asked in an earlier talk during this session, that have analyzed the accuracy of the NCDB, particularly in patients who receive treatment at multiple facilities? Many patients receive radiation at facilities close to their home, which are distinct from the sites where they received operation, often many months after the time of their operation. How accurate is the data collected in a situation such as this? The National Accreditation Program for Breast Centers (NAPBC), has been a highly successful quality program of the American College of Surgeons. Did you observe a difference in patients treated at accredited centers? If so, should your work be a call for centralization of breast cancer care in accredited centers? Quality standard 2.12 of the NAPBC assesses radiation quality based on the percentage of patients receiving whole breast radiation who are less than 70 years old who receive breast-conserving surgery. Should radiation therapy for N2/N3 disease in mastectomy patients be added as a separate component of this quality standard for NAPBC? Some of the very high-risk patients you are describing will develop metastatic disease after surgery and before the start of adjuvant radiation. Adjuvant radiation can often occur 6 to 7 months after surgery. Are these patients accounted for in this study? Would you advocate adjuvant radiation in patients who do develop early metastatic disease? Most patients in our practice who present with N2 or N3 disease are treated with neoadjuvant therapy and with modern neoadjuvant combination therapy in patients with particular subtypes of breast cancer, such as HER2 amplified. Complete nodal response rates of up to 70% can be seen.
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The role of radiation in these patients with complete response is currently the subject of the National Surgical Adjuvant Breast and Bowel Project B-51 study. Does your study include any patients who received neoadjuvant therapy, or were they excluded as part of this analysis? There’s a growing body of evidence that identifies depression among newly diagnosed breast cancer patients, particularly those with advanced stage disease. Depression is associated with treatment noncompliance. Is depression accounted for in the comorbidity index? Do you think it’s being accurately assessed, recorded, or treated? Finally, how do we address the findings to improve outcomes? Are we witnessing a failure of multidisciplinary coordinated care in that patients are not being properly referred or handed off to other specialists after initial treatment? Is this a patient noncompliance issue or is this really a physician education issue? DR KIRBY BLAND (Birmingham, AL): I should note that on an annual basis at the Southern, Dr Ben Li and others of the faculty at LSU-Shreveport have presented papers for studies of the breast cancer population available to the Feist-Weiller Cancer Center, LSU-Shreveport. As noted, the authors have evaluated a large database available from the NCDB reported by the American College of Surgeons and the American Cancer Society to determine the compliance rates of postmastectomy radiation therapy (PMRT) for women that focused on advanced axillary nodal disease (N2/N3). Their conclusions are evident in that a significant portion of their patients (35%) undergoing mastectomy for N2/N3 disease did not receive PMRT. Moreover, the authors have determined that the factors that are not interrelated to this major failure in therapy for advanced disease were age and/or socioeconomic factors (type of facility, location of facility, race/ethnicity, income status, insurance provision, educational level, population density, and the time and distance necessary for travel from home to the radiation therapy facility). Independent factors the authors suggest are predictive for receipt of PRMT include: (1) readmission within 30 days; (2) being a recipient of chemotherapy in the postoperative period; and (3) living status at 30 days postoperatively. While I enjoyed this paper, its implications are considerable in that we are failing nationally in the compliance expectation status for all patients, regardless of diversity, ethnicity, and socioeconomic status. Further, it was particularly concerning to me that 82% of the eligible patients did receive chemotherapy, whereas only 65% of the cohort had PRMT. Thus, I would ask Dr Chu and his colleagues for potential explanations of the failure of one third of patients with N2/N3 disease and methodologies that can be implemented to improve this outcome. 1. The preponderance of patients had health insurance (96.1%), were white (81%), and 83% had a zero comorbidity index. Your data confirmed that the categorical factors associated with the receipt of PMRT had no significant influence on the implementation of radiation therapy postmastectomy. However, univariate factors that do conform and are associated with PMRT compliance include: tumor grade, receipt of
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chemotherapy and hormonal therapy, 30-day mortality, and vital status at last follow-up. These data suggest that patient compliance is influenced by consultation with the surgical oncologist/general surgeon, radiation therapist, and respective oncologist regarding severity of the tumor, the necessity of readmission, and prior administration of chemotherapy or hormonal therapy. This would appear to be, principally, a communication lapse by the physician to initiate therapy and, therefore, failure to initiate compliance. Thus, one would expect that the two-thirds of patients who were compliant with PMRT were provided consultation communication, and the therapy later was acknowledged by the patient to have superior outcomes. What is your consideration? 2. There has been no change in the axillary status staging in the 7th edition of the AJCC Manual on Cancer Staging, edited by one of our members, Dr Rick Greene. Therefore, for more than 4 positive nodes (N2) and more than 10 nodes (N3) status, these categories are stage 3A, B or C. Locoregional recurrence can be reduced by an absolute probability of more than 20e25% with regional postmastectomy radiation therapy, with a slight enhancement of overall survival that approaches 5e10%. Is there data either in the SEER-Medicare database or in the NCDB to sort out the consultation parameters for these patients? It would appear to me that to have this considerable failure for completion of therapy is a major flaw in the consultation with the surgeon at time of postsurgical discharge or in the consultation with the oncologist. How do you explain this and how can this be improved? 3. Using multiple logistic regression analyses, 3 independent predictors of PMRT were identified: (1) chemotherapy; (2) readmission within 30 days of discharge; and (3) survivorship. These factors were the principal determinants for a patient to accept PMRT, if the patient has received a continuum of communication on the importance of additional therapiese chemotherapy, hormonal therapy, radiation therapy–in the postsurgical discharge period. It remains difficult to comprehend why as great as one third of patients failed compliance with this advanced nodal status. What is the authors’ explanation for this major deficiency? 4. Finally, it appears that our comprehensive community cancer centers do a better job than academic teaching centers and the community cancer centers to ensure PMRT compliance. The considerable variance in regional PMRT compliance of greater than 20% is noteworthy, with the highest compliance rates occurring in the Northeast at 68% and lower rates in the West at 47%. Is this strictly a major failure of proper comprehensive consultation with the formative plans of postsurgical therapy? Is it simply a result of follow-up communication, or does this PMRT failure remain an enigma which would require major research efforts, particularly from an epidemiologic/demographic standpoint. DR DAVID OLLILA (Chapel Hill, NC): I practice in 100 counties, and there is very poor distribution of linear accelerators throughout the state. One factor that hasn’t been mentioned at all is actually
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having a linear accelerator in the county where the patient lives. And there’s an old body of literature that shows an increased mastectomy rate if there’s no linear accelerator in the county where the patient resides because it takes time. I would bring a factor in for everyone to consider that, as we talk about multidisciplinary care, it’s very easy to go see the surgeon for an operation and one postoperative visit. But it becomes very, very labor intensive for someone who has to literally drive 3 counties away to get to a radiation facility, Monday through Friday for 5 weeks. I think this is a factor that the NCDB can’t account for, and I would like to hear your input on that situation. DR WILLIAM C WOOD (Atlanta, GA): I would congratulate Dr Chu on bringing a good paper to the Southern raising other questions about our management of breast cancer. He also, with his disclosure statement at the beginning, pointed out one of the problems that we have with access to major data sets today. That is, they must be deidentified before we study them. It would be ideal, I believe, faced with the findings in this study, to biopsy 100 of those patients who did not have radiation and find out if they really did not have radiation or did they have it somewhere else at a distance? Or did they not because they had no access to it, as Dr Ollila has just suggested? Unfortunately, because we are deidentifying all our data for good reasons of privacy, that is not something that can arise from these large data set analyses. DR QUYEN CHU: The accuracy and limitations of the NCDB have been addressed earlier by the previous presenter. I think that the importance of the NCDB is that it helps generate hypotheses so that we can actually identify the problem, examine it, and then move forward in trying to address it. Obviously, our analysis doesn’t answer all the questions. The NCDB does have some limitations, and like any large database, such as the SEER database, the NCDB is prone to inaccuracies such as possible error in data entry, lack of or missing information, and patients being treated at multiple facilities. The question about facility treatment, and patients going from one facility to another, is one of the concerns of the database. The great circle distance is a surrogate marker of access to radiation facility. The definition of great circle distance is the distance between the patient’s residence and the hospital that enters the data. It does not say anything about whether that hospital has a linear accelerator, as Dr Ollila had mentioned. Because of this, I agree with Dr Ollila that that is one of the weaknesses of the paper. Unfortunately, we have no other way of going around it. However, I believe that the heart of the question is access to care. Based on our data, socioeconomic factors, which I think are also a surrogate marker of accessibility to a radiation facility, had no impact on the use of PMRT, either on univariate analysis or multivariate analysis. Therefore, I think that although access to a radiation facility could pose as a potential problem–and we are also facing the same thing down here in Louisiana, since our state is one of the poorest states in the United States. I don’t think access contributes significantly to the lack of PMRT. The question about whether we should use adjuvant radiation therapy in N2/N3 patients as a new surrogate for quality is an
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excellent one. We do know that Commission on Cancer (CoC) tracks the use of radiation therapy after breast conservation therapy for women 70 years of age. But I don’t know whether it tracks for patients with N2/N3 disease. I have heard that it might be one of the quality indicators for the upcoming years. Perhaps our work may serve as a starting point to examine whether PMRT for N2/ N3 disease should also be tracked as a quality measure. Would we recommend PMRT for patients with distant disease? I don’t think that the answer is clear cut because it depends on the clinical situation. I think that not all distant disease behaves in the same manner. Obviously, patients with limited bone metastases may behave differently than those with multiple site of metastases. In such a patient, I might consider PMRT. Obviously, patients with multiple metastases in the bone, liver, and lungs are not likely to die of locoregional recurrence, but rather die of distant disease. For these, I might be more inclined to withhold PMRT. The other question that Dr Bland asked basically stresses the importance of educating the clinicians that PMRT is standard of care for patients with N2/N3 disease. Smith and colleagues from MD Anderson looked at the SEER-Medicare database of patients
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65 years of age and found that the compliance rate for PMRT was roughly 50%. Their thought was that although education and dissemination of information is important, accountability is equally important. They cited that in British Columbia, where there is accountability, the compliance rate for PMRT is around 97%. Perhaps, to improve PMRT compliance rate, I think we might want to consider looking at the use of PMRT as a surrogate of quality for all CoC-designated centers. Dr Bill Wood, I think you made a great comment about the problem with the deidentifier. I think the simplest and direct method to examine the problem is what you have proposed. However, once we embark on that pathway, we will have to go through the IRB. I don’t know about your institution, but the IRBs at our institution are not very user friendly. It is a very laborious process and very painstaking to get even a simple retrospective study approved at our institution. Yes, I believe the idea that you brought up is interesting and provocative, but I’m not sure how we could go about doing that through the CoC or even within our institution.