Comprehensive Cancer Network Centers Research Articles

Abstract 1002: The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials

Abstract The National Comprehensive Cancer Center Network cancer guidelines state that the best management for a cancer patient is on a clinical trial. However, the demographics of 74 registration trials for oral cancer therapies from 2009 - 2019 show only 2.5% of participating patients were Black. Similarly, of the 3,593 patients enrolled in all registration trials for new cancer drugs approved by the FDA in 2019, only 4% were Black patients. A third analysis showed that between 2008 and 2018, only 3.1% of cancer trial patients were Black. The underrepresentation of Black patients in cancer clinical trials is a complex issue that requires a multifaceted solution. Complicated, interdependent causes include, but are not limited to system, provider, and patient bias. Increasing globalization of clinical trials also contributes to a widening gap in Black patient enrollment. Achieving diversity among clinical trial participants requires intention in study design regarding accrual sites and outreach, and involvement of a diverse trial workforce. The ideal clinical trial system would minimize system, provider, and patient biases. Such a system already exists in the Historically Black Colleges and Universities (HBCU) system. HBCUs represent 3% of institutions of higher education in the USA, yet they enroll 16% of Black students and confer 24% of all baccalaureate degrees earned by Black students. 40% of Black engineers, 50% of Black lawyers, 70% of Black physicians, and a staggering 80% of Black judges attended an HBCU. HBCUs are exceptional at impacting communities of Color and have been doing so for centuries. The HBCU Cancer Trials Consortium (HBCU CTC) is a network of HBCUs and Ally institutions that aims to bring innovative cancer clinical trials to historically underserved communities and honor the legacy of HBCUs, which have consistently and successfully served underserved communities for over a century. The HBCU CTC will oversee and conduct cancer clinical trials at member institutions. We envision founding flagship members to include HBCUs that provide graduate medical education and training, such as Howard, Meharry, Charles Drew, and Morehouse. Non-HBCUs committed to the mission are invited to join the consortium as Ally institutions (eg. MSIs). Membership is not exclusive of membership in other cancer consortia. The HBCU CTC will provide shared resource services for member institutions that lack expertise or funding to conduct services locally (eg. data management, DSMB, biostatistics, a cancer focused IRB, central radiology, and central pathology). The Consortium will also work to develop local infrastructure support for the conduct of cancer clinical trials at member institutions. Citation Format: Sheldon L. Holder, Robert A. Winn, Wafik S. El-Deiry. The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1002.

Genomically matched therapy in refractory colorectal cancer according to ESMO Scale for Clinical Actionability of Molecular Targets: experience of a comprehensive cancer center network.

Efficiency of expanded genomic profiling (EGP) programmes in terms of final inclusion of patients in genomically matched therapies is still unknown. Fit patients with advanced and refractory colorectal cancer (CRC) were selected for an EGP programme. Next-generation sequencing (NGS) analysis from formalin-fixed paraffin-embedded tumour samples was performed. The purpose was to describe the prevalence of genomic alterations defined by the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), as well as the percentage of patients finally included in genomically guided clinical trials. In total, 187 patients were recruited. Mutational profile was obtained in 177 patients (10 patients were failure due to insufficient tumour sample), copy number alterations in 41 patients and fusions in 31 patients. ESCAT-defined alterations were detected in 28.8% of the intention-to-analyse population. BRAF V600E was clustered in ESCAT I, with a prevalence of 3.7%, KRAS G12C and ERBB2 amplification were clustered in ESCAT II, whose prevalence was 4.2% and 1.6%, respectively. Most alterations were classified in ESCAT III (mutations in ERBB2, PIK3CA or FGFR genes and MET amplification) and IV (mutations in BRAF non-V600E, ERBB3, FBXW7, NOTCH, RNF43), with a single prevalence under 5%, except for PIK3CA mutation (9%).The final rate of inclusion into genomically guided clinical trials was 2.7%, including therapies targeting BRAF V600E or RNF43 mutations in two patients each, and ERBB2 mutation in one patient. In conclusion, EGP programmes in patients with advanced CRC are feasible and identify a subset of patients with potentially druggable genomic alterations. However, further efforts must be made to increase the rate of patients treated with genomically guided therapies.

Analysis of Hematology and Oncology Fellowship Website Content and Diversity Representation.

Hematology and oncology (HO) lags behind all medicine subspecialties in fellows under-represented in medicine (URM) despite a growing minority patient population. Websites have been effectively used in URM recruitment. We evaluated all US HO program websites to facilitate a more informed and URM-considerate recruitment. We also performed a stratified analysis on programs affiliated with National Cancer Institute (NCI) Designated Cancer Centers, National Comprehensive Cancer Center Network (NCCN) member institutions, and ranked as a top 50 cancer hospital by US News, given their stated commitment to outreach. Websites of all 2019-2020 Accreditation Council for Graduate Medical Education-accredited HO programs were assessed for 28 informational and three diversity categories. Websites with > 70% of categories were comprehensive. Affiliation with NCI, NCCN, and US News was noted. One hundred fifty-six websites were analyzed: 20% were comprehensive and 22% had any diversity information. Inclusion of diversity content and being comprehensive were significantly associated (P = .001). NCI, NCCN, and US News ranking were significantly associated with inclusion of more information in univariate analyses (P < .001, P = .008, and P < .001, respectively). Multivariate analyses showed that US News ranking was significantly associated with more information (P = .005). Diversity-related univariate and multivariate analyses showed a significant association with US News ranking (P = .006 and P = .029, respectively). Most HO fellowship websites are not comprehensive and lack diversity content. Given COVID-19 travel restrictions limit in-person interviews, digital program presence remains an important opportunity. HO programs should offer comprehensive and inclusive websites to better inform applicants, including URM. This may increase institutional diversity and potentially improve URM representation in the HO workforce.

Development of evidence-based clinical pathways for an outpatient oncology acute care clinic.

e18676 Background: Oncology patients frequently experience acute physical symptoms related to cancer and its treatment. Management of symptoms is best accomplished using evidence-based clinical care. When implementing an advanced practice provider (APP)-led oncology acute care clinic, evidence-based clinical pathways were developed to ensure standardization among treating providers. Methods: The top ten emergency department admitting diagnoses for oncology patients identified by the Centers for Medicare and Medicaid Services provided the foundation for development of the clinical pathways. Relevant primary literature, National Comprehensive Cancer Center Network guidelines, and American Society of Clinical Oncology guidelines were reviewed for development of outpatient oncology acute care clinical pathways. The information was cross-referenced with institutional data to confirm applicability to the patient population. A multidisciplinary team including nursing, pharmacy, laboratory services, radiology, information technology, and administrative staff reviewed the workflow to ensure best processes. The pathways were reviewed by oncologists, APPs and pharmacists before finalization. Results: Nine evidence-based clinical pathways were developed by August 1, 2020. From August to December 2020, 165 patient visits took place in the outpatient oncology acute care clinic. Gastrointestinal manifestations (25%), hypovolemia/weakness (25%), and infections (17%) were the most frequently encountered symptoms. Evidence-based clinical pathways were followed for patients with a chief complaint with an associated algorithm (N=124). Conclusions: Implementation of clinical pathways facilitate best practice standardization when ordering labs, tests, and medications while enhancing the acceptance of the new service. The pathways will be reviewed and updated by a multidisciplinary team every 3 months to ensure current evidence-based practices. Semi-annual pathway audits have been implemented to evaluate utilization and optimize patient outcomes, as well as determine areas of improvement and growth. Areas of opportunity identified during the first pathway audit included creating pathways for cardiac disorders, mouth disorders, and infections unrelated to neutropenia. Additionally, order set integration to automate the clinical pathway process in the electronic medical record is in progress.[Table: see text]

Standard Operating Procedures (SOPs) for Palliative Care in German Comprehensive Cancer Centers - an evaluation of the implementation status

BackgroundThe working group for palliative medicine within the Comprehensive Cancer Center (CCC) network funded by the German Cancer Aid in Germany has developed and published 14 Standard Operating Procedures (SOPs) for palliative care in CCCs. This study analyzed to what extent these SOPs have been implemented in the clinical routine in the CCC network one year after their publication.MethodsAn online-based survey on the implementation status, limitations in daily practice and further themes was conducted between April and July 2018. In total, 125 health professionals in specialized palliative care from all 16 CCC locations were invited to participate. The data were analyzed descriptively using SPSS.ResultsThe response rate was 52.8%. More than half of the respondents (57.6%) knew about the free availability of SOPs on the CCC network website. The extent to which each SOP was being used actively in practice by the survey respondents ranged from a low of 22.7% (for the “Fatigue” SOP) to a highest of 48.5% (for the “Palliative Sedation” and “Respiratory Distress” SOPs). The respondents became aware of the SOP through recommendations from colleagues, team meetings or from the head of the department. The SOPs “Respiratory distress of an adult palliative patient” and “Palliative sedation” were perceived as the most practically oriented and understandable. Barriers to use SOPs were mainly limited time resources and lack of knowledge of existence and availability.ConclusionsIn practice, better knowledge about the SOPs and at the same time increased use can be achieved through systematic training or discussion of SOPs in regular team meetings. There is a need to take measures to optimize the implementation in clinical practice.

Impact of preoperative prostate magnetic resonance imaging on the surgical management of high-risk prostate cancer

ObjectiveTo evaluate the effect of adding multiparametric magnetic resonance imaging (mpMRI) to pre-surgical planning on surgical decision making for the management of high-risk prostate cancer (HRPC).Patients and methodsA survey was designed to query multiple centers on surgical decisions of 41 consecutive HRPC cases seen from 2012 to 2015. HRPC was defined by the National Comprehensive Cancer Center Network guidelines. Six fellowship-trained urologic oncologists were asked for their surgical plan in regards to the degree of planned nerve-sparing and lymph node dissection. Two rounds of surveys were administered to six external urologic oncologists. The first survey included the case description only and the second included case description with mpMRI images and report. The correct surgical plan was analyzed by correlation of the degree of planned surgical excision and consistency with the final pathologic evaluation. A priori, an effect size of 20% change was used to determine statistical significance, at p < 0.05.ResultsAll cases had at least one change to surgical planning after mpMRI review. Forty (98%) patients had a change in the degree of planned nerve sparing: wider excision in 32% and increased nerve sparing in 24%. After mpMRI the correct surgical plan change was made in 49% for the right and left 51%, decreasing the potential for positive margins. Lymph node dissection was altered from standard to extended lymph node dissection in 17%.ConclusionsAlthough mpMRI is not integrated in guidelines for preoperative planning in HRPC, its use may impact surgical planning, cancer control, and quality of life.

System-Level Factors Associated With Use of Outpatient Specialty Palliative Care Among Patients With Advanced Cancer.

The proportion of patients with advanced cancer who receive outpatient specialty palliative care (OSPC) is as low as 2.0%. Improved understanding of the system-level factors influencing use of OSPC could inform adaptations to the delivery of palliative care to maximize access. We examined associations between OSPC use among patients with advanced solid tumors and oncology-OSPC clinic colocation and patient travel time to an OSPC clinic. We conducted a retrospective cohort study of patients with advanced solid tumors receiving oncologic treatment between January 1 and December 31, 2016, within a comprehensive cancer center network with well-established, oncology-specific OSPC clinics. Multivariable logistic regression analysis was used to evaluate the associations of clinic colocation and geographic access with OSPC use. Of 9,485 patients with advanced solid tumors, 478 (5.0%) received OSPC services in 2016. After controlling for age, sex, marital status, cancer type, insurance, treatment intent, and illness severity, patients whose oncologist practices were colocated with OSPC clinics were more likely to use OSPC (odds ratio [OR], 19.2; 95% CI, 14.1 to 26.2). Compared with patients who lived > 90 minutes from an OSPC clinic, patients with travel times of < 30 minutes (OR, 3.2; 95% CI, 2.2 to 4.6) and 31 to 60 minutes (OR, 2.4; 95% CI, 1.6 to 3.6) were also more likely to use OSPC. Among patients with advanced solid tumors, colocation of oncology and OSPC clinics and shorter patient travel time were associated with greater odds of using OSPC. Future efforts to increase OSPC use in this population should consider clinic colocation and travel burden.

Integration of Palliative Care into the Comprehensive Cancer Center of Germany - Consultation Hours and Fellowship Rotations of the Specialized Palliative Care

Comprehensive Cancer Centers are characterized by interdisciplinary exchange for meeting increasingly complex care needs during the course of the disease. Tumor consultations hours and fellowship rotations build hereby bridges between the subjects and disciplines. In order to be able to provide support in the Comprehensive Cancer Center Network for the further integration of specialized palliative medicine, it was highlighted to what extent consultation hours and fellowship rotations for the palliative care are integrated into the centers. Information about the spS and fellowship rotation of the Comprehensive Cancer Center (n = 16), which had previously been funded by the Cancer Aid, was paper-based collected with a survey questionnaire. For this purpose, the heads of the palliative care departments of the centers were interviewed from July to August 2017. The evaluation was performed by SPSS (frequency, mean value, median, range). 15 from 16 centers responded to the survey (93.75 %). Nine centers (60 %) have a consultation hour for palliative care. Four from nine centers can submit this offer for ≥ 4 hours (44.4 %). Fellowship rotations in the palliative care occur primarily in all centers from oncology / hematology (n = 11, 73.3 %) and anaesthesia (n = 6) and often for a twelve months (n = 11) period of time. Outpatient structures of the palliative care have been insufficiently implemented to a consultation hour within Comprehensive Cancer Centers. The existing effort to integrate palliative care into the oncological course of disease requires further structuring in order to increase the visibility of palliative care services. Fellowship rotations in the palliative care department are regularly implemented in the network even if only for some of the subjects in order to raise awareness of the possibilities of the palliative care.

Standardization of Radiation Therapy Dose for Locally-Advanced Non-Small Cell Lung Cancer (NSCLC) through Changes to a Lung Cancer Clinical Pathway in Large Network

The initial results of RTOG 0617 which randomized patients with Stages IIIA/IIIB NSCLC to definitive chemoradiotherapy (CRT) to a maximum dose of 60 Gy vs. 74 Gy suggested no benefit to the high-dose arm. Final results demonstrated a detrimental survival impact with high-dose RT. Clinical pathways (CP) standardize care when many therapeutic options exist and clinical practice varies unnecessarily. We evaluated the impact of changes to a CP guiding management of NSCLC on practice patterns throughout a large, integrated comprehensive cancer center network. In 2003, we implemented a CP for management of Stage IIIA/IIIB NSCLC with definitive CRT. In 2009, we required entry of treatment decisions into an online clinical physician decision support tool integrated with medical records to track CP choices. Off-pathway selections were subject to peer review. In June 2013, the CP for NSCLC was amended (amendment 1) to allow a dose range of 60-74 Gy with heterogeneity correction, reflecting the two arms of 0617. The CP was again changed (amendment 2) in January 2016 to specify a dose range of 60-70 Gy, and higher doses were considered off-pathway and subject to peer review. Data from treatment decisions entered from January 2012 to September 2016 were obtained. From 2012 until final publication of 0617 in February 2015, 367 treatment decisions were entered. The median prescription dose was 66 Gy (range, 54.0-79.8) delivered in 1.8-2.1 Gy fractions. Doses <66 Gy were prescribed for 190 patients (52%). From February 2015 to September 2016, 211 treatment decisions were entered. The median prescription RT dose was 60 Gy (range, 60-76). Prior to amendment 2, 117 (91%) of 128 prescription doses were <66 Gy. After amendment 2, 82 (99%) of 83 decisions were <66 Gy. Stage of disease was not associated with dose <66 Gy (p=0.984). Dose <66 Gy was associated with treatment following publication of 0617 (p<0.001) and treatment after amendment 2 (p<0.001), though on multivariate analysis, only treatment after amendment 2 was associated with dose <66 Gy (OR 9.9, 95% CI 5.2-19.0, P<0.001). The overall median heart V40 Gy and lung V20 Gy were 4.3% (range 0-36.0) and 25.7% (range 4.1-44.5), respectively. Lung V20 Gy was lower following publication of 0617 (median 23.4%) than before (median 28.8%) (p<0.001), but there was no difference in heart V40 Gy (p=0.70). CP’s translate published research and institutional experience into standardized patient management plans to promote evidence-based care and eliminate inefficient variations in practice patterns that lead to inferior outcomes. Recognizing that our CP for definitive treatment of patients with locally-advanced NSCLC allowed heterogeneous dose prescriptions, we modified the CP based upon the final publication of RTOG 0617. We found that the CP was a powerful tool to ensure patients receive consistent high-quality, evidence-based care.

High Rates of Minimally Invasive Hysterectomy Surgery for Endometrial Cancer at National Comprehensive Cancer Network Centers

High Rates of Minimally Invasive Hysterectomy Surgery for Endometrial Cancer at National Comprehensive Cancer Network Centers

Standardization of radiation therapy dose for locally advanced non-small cell lung cancer through changes to a lung cancer clinical pathway in a large, integrated comprehensive cancer center network

PurposeThe results of Radiation Therapy Oncology Group (RTOG) 0617, which randomized patients with stages IIIA/IIIB non-small cell lung cancer (NSCLC) to definitive chemoradiation therapy to 60 Gy versus 74 Gy, demonstrated a detrimental survival impact with high-dose radiation therapy. We evaluated the impact of changes to a provider-driven clinical pathway (CP) guiding management of NSCLC on practice throughout our cancer center network. Methods and materialsIn 2001, we implemented a CP for management of stage IIIA/IIIB NSCLC with definitive chemoradiation therapy. In 2013, the CP for NSCLC was amended (amendment 1) to allow a dose range of 60 to 74 Gy. The CP was amended (amendment 2) in January 2016 to specify a dose range of 60 to 70 Gy. Higher doses were considered off-pathway and subject to peer review. Data from decisions entered from 2012 to 2016 were obtained. ResultsFrom 2012 until publication of RTOG 0617 in February 2015, the median prescription dose was 66 Gy delivered in 1.8 to 2.1 Gy fractions. Doses ≤66 Gy were prescribed for 52% of patients. From February 2015 to September 2016, the median prescription dose was 60 Gy, and 91% of prescription doses were ≤66 Gy. After amendment 2, 99% of decisions were ≤66 Gy. Dose ≤66 Gy was associated with treatment following publication of 0617 (P < .001) and treatment after amendment 2 (P < .001). On multivariable analysis, treatment after amendment 2 was associated with dose ≤66 Gy (odds ratio, 9.9; 95% confidence interval, 5.2-19.0; P < .001). The percentage of lung receiving 20 Gy was lower following publication of 0617 (P < .001). There was no difference in the percentage of heart receiving 40 Gy. ConclusionsCPs eliminate variations in practice that lead to inferior outcomes. Recognizing that our CP for definitive treatment of patients with locally advanced NSCLC allowed heterogeneous dose prescriptions, we modified the CP based on the publication of RTOG 0617. We found that the CP was a tool to ensure patients receive evidence-based care across a large cancer center network.

Standardization of Radiation Therapy Dose for Locally Advanced Non–Small Cell Lung Cancer Through Changes to a Lung Cancer Clinical Pathway in a Large, Integrated Comprehensive CancerCenter Network

Standardization of Radiation Therapy Dose for Locally Advanced Non–Small Cell Lung Cancer Through Changes to a Lung Cancer Clinical Pathway in a Large, Integrated Comprehensive CancerCenter Network

Abstract P1-10-16: Standardization of nodal radiation therapy (RT) through changes to a breast cancer clinical pathway (CP) in a large, integrated comprehensive cancer center network

Abstract Purpose The efficacy of adjuvant RT following breast conserving surgery (BCS) in reducing risk of local recurrence is established. The results of Z11, AMAROS and MA-20 studies led to wide variation in RT treatment volume for patients (pts) who have sentinel node biopsy positive disease. CP's are a mechanism of standardizing care when many therapeutic options exist and clinical practice varies unnecessarily. We sought to evaluate the impact of changes to a CP guiding adjuvant RT in sentinel node positive pts for invasive breast cancer (IBC) on practice patterns throughout a large cancer network. Methods In 2003, we implemented a CP for management of IBC with adjuvant RT. In 2009, we required entry of management decisions into an online tool integrated with medical records to track CP choices and subject off-pathway selections to peer-review. The CP for treatment of pts with positive sentinel lymph nodes (LN) following BCS was modified in February 2015 to promote uniform treatment of regional LN irradiation (RNI). In summary, the CP recommended modified tangents (MT) including level 1 and 2 nodes for all pts with micrometastases. For pts with macrometastases, CP recommended including level 1 and 2 LN in MT and add additional field to include level 3, supraclavicular LN +/- IM node for pts with any adverse factor present defined as T2 disease, LVSI, high grade, ER negative, ECE or premenopausal pts. Data from treatment decisions entered into the support tool from June 2009 to April 2016 were obtained. Results From 2009 until CP modification in 2015, 1089 treatment decisions were entered. Decisions were heterogeneous and included 24 distinct options. Following pathway amendment, 178 decisions were entered. Three pts were enrolled in clinical trials &amp; 9 referred to other providers and excluded. Of the remaining 166 pts, 7 (4.2%) were treated off pathway for poor performance status, patient preference, or gross residual disease. The 159 (95.8%) on-pathway pts were analyzed. Median age was 61 (range 32-90) years. All pts underwent BCS for IBC and had positive sentinel LN. Forty-four (27.7%) pts had micrometastastatic LN disease, and 115 (72.3%) had macrometastases, of which 82 (71.3%) had adverse risk factors. All 44 pts with micrometastases were treated with MT. Six (5.2%) pts with macrometastases were treated with WBT RT, 33 (28.7%) with MT, &amp; 76 (66.1%) with MT and a 3rd field. Seventy-six (92.7%) pts with adverse risk factors were treated with MT and 3rd field (p&amp;lt;0.001). Conclusions CP's are useful tools for translating published research, national guidelines, and institutional experience into standardized patient management plans to promote evidence-based care and eliminate unnecessary variations in practice patterns that lead to inefficiency and inferior outcomes. Recognizing that our CP for adjuvant treatment of patients with positive sentinel LNs undergoing BCS allowed heterogeneous treatment selections, we modified the CP in 2015 based upon the latest evidence regarding RNI. We found that following the amendment, patients received RT fields guided by the CP leading to more standardized treatment based upon clinical risk factors and facilitating tracking of patient outcomes. Citation Format: Gebhardt BJ, Horne ZD, Heron DE, Beriwal S. Standardization of nodal radiation therapy (RT) through changes to a breast cancer clinical pathway (CP) in a large, integrated comprehensive cancer center network [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-16.

Abstract P2-08-01: Prospective trial of endocrine therapy alone in patients with estrogen receptor positive, HER2-negative, node-negative breast cancer: Results of the TAILORx low risk registry

Abstract Background: The Trial Assigning Individualized Options for Treatment (TAILORx) is a prospective trial evaluating the role of endocrine therapy or chemoendocrine therapy in patients 18-75 years of age with estrogen receptor (ER)-positive, HER2-negative breast cancer, a primary tumor between 0.6-5.0 cm, and negative axillary nodes, a population for whom chemotherapy is typically recommended or least considered based on National Comprehensive Cancer Center Network (NCCN) guidelines. Methods: The trial was designed to demonstrate non-inferiority of endocrine therapy compared with chemoendocrine therapy in the randomized group with an Oncotype DX Recurrence Score (RS) of 11-25. Patients with a low RS &amp;lt; 11 were assigned to endocrine therapy alone and with a high RS &amp;gt; 25 assigned to chemoendocrine therapy, and both groups were followed in a prospective registry. The definition of an intermediate RS differed in this trial (RS 11-25) from the original reports (RS 18-30) in order to reduce the risk of chemotherapy undertreatment in patients with a mid-range or low RS (Sparano &amp; Paik. J Clin Oncol 2008; 26:721-728). Results: The trial enrolled 10,273 patients between April 2006 and October 2010, of whom 6907 patients (67.2%) had a mid-range RS of 11-25, 1737 (16.9%) had a high RS &amp;gt; 25, and 1639 (15.9%) had a low RS of &amp;lt; 11. At the fourth planned interim analysis, the ECOG-ACRIN data monitoring committee recommended that the study continue as planned for the randomized group with a RS 11-25, and that the results be released to the investigators for the low risk group with a RS &amp;lt;11. The characteristics of the low risk registry population are as follows: age 50 or less (27%), 51-60 (35%), &amp;gt; 60 (39%); tumor size &amp;lt; 1 cm (8%), 1-2 cm (61%), &amp;gt; 2 cm (31%); histologic grade low (34%), intermediate (59%), high (7%); breast conservation (68%) or mastectomy (32%). Initial endocrine therapy included tamoxifen in 35%, aromatase inhibitors in 59%, ovarian function suppression in 3%, and unspecified therapy in 3%; 5 patients received adjuvant chemotherapy (1 of whom relapsed). Five-year rates (and 95% confidence intervals [CI]) for low RS group were 99.2% (98.5, 99.6%) for distant relapse free interval, 98.5% (97.7, 99.1%) for relapse-free interval, 93.7% (92.2, 94.9%) for invasive disease free survival, and 98.2% (97.3, 98.7%) for overall survival. Information regarding ER, PR, and HER2 RNA expression will be presented. Conclusions: Despite meeting guidelines for recommending or at least considering adjuvant chemotherapy based on classical clinicopathologic features, the risk of recurrence was very low at 5 years in patients with ER-positive, HER2-negative, axillary node-negative breast cancer and a low RS of &amp;lt; 11 treated with endocrine therapy alone without chemotherapy. Citation Format: Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer Jr CE, Dees EC, Perez EA, Olson Jr JA, Zujweski J, Keane MM, Gomez Moreno HL, Reddi RP, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge Jr GW. Prospective trial of endocrine therapy alone in patients with estrogen receptor positive, HER2-negative, node-negative breast cancer: Results of the TAILORx low risk registry. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-01.

The Impact of Dynamic Changes to a Bone Metastases Pathway in a Large Integrated National Cancer Institute Designated Comprehensive Cancer Center Network

The Impact of Dynamic Changes to a Bone Metastases Pathway in a Large Integrated National Cancer Institute Designated Comprehensive Cancer Center Network

Impact of dynamic changes to a bone metastases pathway in a large, integrated, National Cancer Institute–designated comprehensive cancer center network

PurposeStudies suggest equivalent pain relief from bone metastases after radiation therapy with >10-fraction regimens and shorter courses. Although American Society for Radiation Oncology evidence-based guidelines and the Choosing Wisely campaign endorse single-fraction treatments and caution against the use of extended courses, publications report single-fraction utilization rates below 5%. We evaluated the impact of our bone metastasis clinical pathway on the adoption of short-course palliative radiation in a large, integrated radiation oncology network. Methods and materialsWe implemented a clinical pathway for the management of bone metastases in 2003 that required the entry of management decisions into an online tool that subjected off-pathway choices to peer review beginning in 2009. In 2014, the pathway was modified to encourage single-fraction treatments, and the use of >10 fractions was considered off pathway. Data were obtained from 16 integrated sites (4 academic, 12 community) from 2003 through 2014. Multivariate logistic regression was conducted to establish factors associated with treatment with a single fraction and with >10 fractions. ResultsIn this study, 12,678 unique courses were delivered. From 2003 to 2008, the single-fraction utilization rate was 7.6%. This increased to 10.9% from 2009 to 2013 and to 15.8% in 2014. The odds ratios for single-fraction use were 1.59 (95% confidence interval [CI], 1.39-1.81) and 2.58 (95% CI, 2.11-3.15) for 2009-2013 and 2014, respectively. Academic physicians were more likely to treat with a single fraction (odds ratio, 5.00; 95% CI, 4.38-5.71). Use of >10-fraction regimens significantly decreased from 18.6% in 2003-2008 to 15.2% in 2009-2013 and 9.7% in 2014. ConclusionsAlthough our single-fraction utilization rate was initially in line with national rates (7.6%), the adoption rate increased to >15%. The use of >10-fraction regimens decreased significantly, predominantly among community practices. By 2014, >90% of courses were delivered with <10 fractions. This study demonstrates that provider-driven clinical pathways are able to standardize practice patterns and promote change consistent with evidence-based guidelines.

Cost-effectiveness analysis of prognostic gene expression signature-based stratification of early breast cancer patients.

BackgroundThe individual risk of recurrence in hormone receptor-positive primary breast cancer patients determines whether adjuvant endocrine therapy should be combined with chemotherapy. Clinicopathological parameters and molecular tests such as EndoPredict® (EPclin) can support decision making in patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative cancer.ObjectiveUsing a life-long Markov state transition model, we determined the health economic impact and incremental cost effectiveness of EPclin-based risk stratification in combination with clinical guidelines [German-S3, National Comprehensive Cancer Center Network (NCCN), and St. Gallen] to decide on chemotherapy use.MethodsInformation on overall and metastasis-free survival came from Austrian Breast & Colorectal Cancer Study Group clinical trials 6/8 (n = 1,619) and published literature. Effectiveness was assessed as quality-adjusted life-years (QALYs). Costs (2010) were assessed from a German third-party payer perspective.ResultsLifetime costs per patient ranged from €28,268 (St.Gallen and EPclin) to €33,756 (NCCN). Due to an imperfect prognostic value and differences in chemotherapy use, strategies achieved between 13.165 QALYs (NCCN) and 13.173 QALYs (EPclin alone) per patient. Using German-S3 as reference, three strategies showed dominant results (St. Gallen and EPclin, German-S3 and EPclin, EPclin alone). Compared to German-S3, the addition of EPclin saved €3,388 and gained 0.002 QALYs per patient. Combining guidelines with EPclin remained preferable in sensitivity analysis.ConclusionOur study suggests that molecular markers can be sensibly combined with clinical guidelines to determine the risk profile of adjuvant breast cancer patients. Compared with the current German best practice (German-S3), combinations of EPclin with the St. Gallen, German-S3 or NCCN guideline and EPclin alone were dominant from the perspective of the German healthcare system.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-014-0227-x) contains supplementary material, which is available to authorized users.

Quantitative evaluation of radiation oncologists’ adaptability to lower reimbursing treatment programs

PurposeRapid development of sophisticated modalities has challenged radiation oncologists to evaluate workflow and care delivery processes. Our study assesses treatment modality use and willingness to alter management with anticipated limitations in reimbursement and resources. Methods and materialsA web-based survey was sent to 43 radiation oncologists in a National Cancer Institute–designated comprehensive cancer center network. The survey contained 7 clinical cases with various acceptable treatment options based on our institutional clinical pathways. Each case was presented in 3 modules with varying situations: (1) unlimited resources with current reimbursement, (2) restricted reimbursement (bundled payment), and (3) both restricted reimbursement and resources. Reimbursement rates were based on the 2013 Medicare fee schedule. Adoption of lower reimbursing options (LROs) was defined as the percentage of scenarios in which a respondent selected an LRO compared with baseline. ResultsForty-three physicians completed the survey, 11 (26%) at academic and 32 (74%) at community facilities. When bundled payment was imposed (module 1 vs 2), an increase in willingness to adopt LROs was observed (median 11.1%). When physicians were limited to both bundled payment and resource restriction, adoption of LROs was more pronounced (module 1 vs 3; median 22.2%, P < .01). There was a trend to selecting LROs between module 1 and 2 that reached significance when transitioning from module 1 to 3. A positive correlation between years in clinical practice and adoption of LROs was demonstrated (r2 = 0.181, P<.01). This association remained significant when stratifying respondents by experience (≤25 vs >25 years, P = .02). ConclusionsRadiation oncologists were more likely to choose lower reimbursing treatment options when both resource restriction and bundled payment were presented. Those with fewer years of clinical practice were less inclined to alter management, perhaps reflecting modern residency training. Future cost-utility analyses may help to better guide radiation oncologists in selection of LROs.

EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer

BackgroundIn early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed.Patients and methodsWe assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan–Meier survival analysis.ResultsAfter 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%–61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years.ConclusionThe EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.

Unsupported off-label chemotherapy in metastatic colon cancer.

BackgroundNewer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use.MethodsWe conducted a retrospective cohort study using commercial insurance claims from UnitedHealthcare, and identified incident cases of metastatic colon cancer (mCC) from July 2007 through April 2010. We evaluated the use of three regimens with recommendations against their use in the National Comprehensive Cancer Center Network Guidelines, a commonly used standard of care: 1) bevacizumab beyond progression; 2) single agent capecitabine as a salvage therapy after failure on a fluoropyridimidine-containing regimen; 3) panitumumab or cetuximab after progression on a prior epidermal growth factor receptor antibody. We performed sensitivity analyses of key assumptions regarding cohort selection. Costs from a payer perspective were estimated using the average sales price for the entire duration and based on the number of claims.ResultsA total of 7642 patients with incident colon cancer were identified, of which 1041 (14%) had mCC. Of those, 139 (13%) potentially received at least one of the three unsupported off-label (UOL) therapies; capecitabine was administered to 121 patients and 49 (40%) likely received it outside of clinical guidelines, at an estimated cost of $718,000 for 218 claims. Thirty-eight patients received panitumumab and six patients (16%) received it after being on cetuximab at least two months, at an estimated cost of $69,500 for 19 claims. Bevacizumab was administered to 884 patients. Of those, 90 (10%) patients received it outside of clinical guidelines, at an estimated costs of $1.34 million for 636 claims.ConclusionsIn a large privately insured mCC cohort, a substantial number of patients potentially received UOL treatment. The economic costs and treatment toxicities of these therapies warrant increased efforts to stem their use in settings lacking sufficient scientific evidence.