Ballman, Karla V.

Purpose The seventh edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer differentiates patients with T1 tumors and lymph node micrometastases (stage IB) from patients with T1 tumors and negative nodes (stage IA). This study was undertaken to determine the utility of the stage IB designation. Patients and Methods The following two cohorts of patients with breast cancer were identified: 3,474 patients treated at The University of Texas MD Anderson Cancer Center from 1993 to 2007 and 4,590 patients from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial. Clinicopathologic and outcomes data were recorded, and disease was staged according to the seventh edition AJCC staging system. Recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results Median follow-up times were 6.1 years and 9.0 years for the MD Anderson Cancer Center and ACOSOG cohorts, respectively. In both cohorts, there were no significant differences between patients with stage IA and stage IB disease in 5- or 10-year RFS, DSS, or OS. Estrogen receptor (ER) status and grade significantly stratified patients with stage I disease with respect to RFS, DSS, and OS. Conclusion Among patients with T1 breast cancer, individuals with micrometastases and those with negative nodes have similar survival outcomes. ER status and grade are better discriminants of survival than the presence of small-volume nodal metastases. In preparing the next edition of the AJCC staging system, consideration should be given to eliminating the stage IB designation and incorporating biologic factors.

Comorbidity was associated with shorter overall survival but not toxicity or relapse among older women with breast cancer with good functional status.

Purpose ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. Methods We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Results Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Conclusion Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

Abstract Background: Fluoro-deoxyglucose positron emission tomography (FDG-PET) scans are used for diagnosis and staging of known or suspected non-small cell lung cancer (NSCLC). Single institution studies examining the impact of avidity on survival have reported mixed results. The purpose of this study is to evaluate the association between FDG-PET avidity and survival in the national prospective ACOSOG Z4031 trial in patients with pathological Stage I NSCLC. Methods: Between 2004 and 2006, 1074 patients with known or suspected clinical stage I (cT1-2N0M0) NSCLC were enrolled in the ACOSOG Z4031 trial and underwent surgical resection. FDG-PET results were abstracted from radiology interpretations included in the case report forms. FDG-PET avidity was categorized based on either radiologist description or reported maximum standard uptake value (SUV). The four categories were: 1) not avid and not cancerous (SUV=0), 2) low avidity and likely not cancerous (SUV&gt;0 and &lt;2.5), 3) avid and probably cancerous (SUV≥2.5 and &lt;5) and 4) highly avid and likely cancerous (SUV≥5). The lesion was classified as avid if in categories 3 or 4. The final diagnosis was determined by pathological examination and all cause mortality was reported. Cox proportional hazard regression was used to assess the impact of FDG-PET avidity on survival. The covariates used in the model included pStage, gender, age, race, and preoperative lesion size. Kaplan-Meier survival curves were calculated and the log-rank test was used to determine differences in survival based on FDG-PET avidity. Results: There were 51 enrolling sites in 39 cities with 969 eligible participants. Preoperative FDG-PET results were available for 540 participants with NSCLC and 81% had FDG-PET avid or highly avid lesions. 400 patients had pStage I NSCLC and the 5 year survival was 70% with 95%CI (65%, 75%). FDG-PET avidity, male gender, age, and lesion size negatively impacted survival. FDG-PET avidity in pStage I disease still negatively impacted survival (p=0.03) when controlling for lesion size. The 5 year survival for Stage I disease was 80% with 95%CI (68%, 88%) in FDG-PET negative patients and 67% with 95% CI (61%, 72%) in FDG-PET positive patients (p=0.02). Conclusions: In a national surgical population with pathological stage I NSCLC, FDG-PET avidity negatively impacted five year survival, independently of lesion size. Further work should be done to determine if chemotherapy would be beneficial in patients with PET avid lesions and pStage I NSCLC. Citation Format: Eric L. Grogan, Stephen A. Deppen, Heidi Chen, Karla V. Ballman, Francys C. Verdial, Melinda C. Aldrich, Paul A. Decker, David H. Harpole, Robert J. Cerfolio, Robert J. Keenan, David R. Jones, Thomas A. D'Amico, Joseph B. Shrager, Bryan F. Meyers, Joe B. Putnam. FDG-PET avidity negatively impacts survival in pStage I NSCLC in the ACOSOG Z4031 trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-296. doi:10.1158/1538-7445.AM2013-LB-296

Abstract Purpose/Objective: The landmark ACOSOG Z0011 trial established that axillary lymph node dissection (ALND) is unnecessary in breast cancer patients with one or two positive sentinel lymph nodes (SLN) who undergo lumpectomy, radiation therapy (RT) and systemic therapy. At a median follow-up of 6.3 years there were no differences in overall survival or local-regional recurrences between patients receiving ALND or SLN biopsy alone. The protocol required whole breast RT using standard tangential fields, but the extent of RT coverage of the regional nodes in these patients has not previously been described. We sought to ascertain this information. Methods: The RT data on the ACOSOG Z0011 trial was collected from case report forms completed by enrolling providers 18 months after enrollment. The response options on the forms included breast, supraclavicular, & other. We reviewed these data and, in 2011-2013, we attempted to identify and contact all treating radiation oncology practices to request detailed radiation treatment records for central review. RT data was sent to the Quality Assurance Review Center (QARC) and reviewed by two independent radiation oncologists, blinded regarding the arm to which the patients were randomized. Results: Of the 891 patients enrolled on Z0011, 35 withdrew consent prior to surgery, leaving 856 who were analyzed in the primary report on trial outcomes.1 Among the 605 of these patients with a completed adjuvant radiation therapy form, 89% were noted to receive whole breast RT. Of these, 89 patients (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were received on 228 patients: 104/389 (26.7%) and 124/404 (30.7%) on the ALND and SLND arms, respectively. Of the 228 patients, 185 patients (81.1%) received tangent-only treatment. Among these 185 patients, there was sufficient data to evaluate tangent field height in 142 (76.8%). High tangent RT fields (with cranial tangent border within 2 cm of the humeral head) were used in 52.6% (40/76) patients randomized to the ALND arm and 50% (33/66) patients randomized to the SLND arm. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥3 fields: 22 in the ALND and 21 in the SLND arm. Those receiving directed nodal RT tended to have greater nodal involvement (p&lt;0.001). Conclusions: Most patients treated on the Z0011 trial received tangential field RT alone, and some received no radiotherapy at all. Some patients received directed nodal irradiation via a third field. In a subgroup for whom detailed RT records were available, the highest rates of directed nodal irradiation were among those with multiple nodes involved. As survival rates and local-regional recurrences were similar in the study arms, no conclusions can be drawn from this analysis on whether this additional radiation treatment was necessary or beneficial. 1JAMA 2011; 305 (6): 569-575. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-19.

A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer.

Abstract Patients with HER2+ breast cancer treated with trastuzumab and chemotherapy have superior survival compared with patients treated with chemotherapy alone. Polymorphisms within FCGR2A and FCGR3A are associated with binding affinity of natural killer cells to the IgG1 portion of trastuzumab, and a polymorphism in FCGR2B (I232T) is associated with impaired regulatory activity. The association of these polymorphisms with clinical response among trastuzumab-treated patients is equivocal, with both positive and negative associations. We performed genotyping analysis on the FCGR3A V158F, FCGR2A R131H, and FCGR2B I232T polymorphisms in 1,325 patients from the N9831 clinical trial. Patients in arm A (N = 419) received chemotherapy only. Patients in arms B (N = 469) and C (N = 437) were treated with chemotherapy and trastuzumab (sequentially in arm B and concurrently in arm C). Using log-rank test and Cox proportional hazard models, we compared disease-free survival (DFS) among genotypic groups within pooled arms B/C. We found no differences in DFS between trastuzumab-treated patients who had the FCGR3A 158 V/V and/or FCGR2A 131 H/H high-affinity genotypes and patients without those genotypes. Furthermore, there was no significant interaction between FCGR3A and FCGR2A and treatment. However, there was a difference in DFS for FCGR2B I232T, with I/I patients deriving benefit from trastuzumab (P &lt; 0.001), compared with the T carriers who did not (P = 0.81). The interaction between FCGR2B genotype and treatment was statistically significant (P = 0.03). Our analysis did not reveal an association between FcγR high-affinity genotypes and outcomes. However, it seems that the FCGR2B inhibitory gene may be predictive of adjuvant trastuzumab benefit. Cancer Immunol Res; 2(10); 962–9. ©2014 AACR.

BACKGROUNDLittle is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib.METHODSRisk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high‐risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months.RESULTSFive factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence‐free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5‐year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P < .001 for each comparison).CONCLUSIONSThe scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence. Cancer 2014;120:2325–2333 © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.