Neoadjuvant Therapy For Stage Research Articles

Clinical outcomes after 1 versus 2-3 lines of neoadjuvant therapy in stage III inflammatory breast cancer.

Many stage III inflammatory breast cancer (IBC) patients experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to allow surgery, while some require additional NAC. We evaluated the pathologic complete response (pCR), breast cancer-free survival (BCFS) and overall survival (OS) among patients requiring 1 vs. 2-3 lines (L) of NAC prior to surgery. Stage III IBC patients from 2 institutions who received 1L or 2-3L of NAC prior to surgery were identified. Hormone receptor and HER2 status, grade, and pCR were evaluated. BCFS and OS were evaluated by the Kaplan-Meier method. Multivariable Cox models were utilized to estimate the hazard ratio (HR). 808 eligible patients (1997-2020) were identified (median age 51years, median follow-up 69months). 733 (91%) had 1L and 75 (9%) had 2-3L of NAC. Grade III, triple-negative and HER2-positive disease were more prevalent in 2-3L patients. 178 (24%) 1L and 14 (19%) 2-3L patients had pCR. 376 1L patients and 41 2-3L patients had recurrences. The 5-year BCFS was worse for the 2-3L group (33 vs. 46%, HR = 1.37; 95% CI 0.99-1.91). However, in 192 patients with a pCR, BCFS was similar (76 vs. 83% in 1L vs. 2-3L, respectively). There were 308 deaths (276 among 1L and 32 among 2-3L patients). The 5-year OS in 1L vs. 2-3L was 60 vs. 53% (HR = 1.32, 95% CI 0.91-1.93). Among stage III IBC patients, pCR rates were similar, irrespective of the NAC lines number, and BCFS and OS were comparable with pCR after 1L and 2-3L.

Temporal Variation of Treatment Patterns and Survival Outcomes of Triple-Negative Breast Cancer Patients: A Real-World Experience From 2000 to 2014

BackgroundPrevious studies have reported a higher prevalence of triple-negative breast cancer (TNBC) in US Hispanic/Latina populations. However, survival outcomes and treatment approaches over time in Latin American females are scarcely reported. We aimed to evaluate the temporal variation in treatment patterns and overall survival (OS) outcomes of females with TNBC according to cancer stage. Materials and MethodsWe performed a single-center retrospective cohort study on 1840 females from 2000 to 2014. Patients were classified in 3 calendar periods (2000-2004, 2005-2009, and 2010-2014). The Kaplan-Meier method and multivariable regression analyses were employed. ResultsStage III cancer was identified in half of the population. Five-year OS estimates for cancer stages I, II, and IV remained unchanged across all calendar periods. However, we found worsening 5-year OS estimates in stage III females (49% in 2000-2004 and 31% in 2010-2014; P < .001). Despite increased uptake of overall use of neoadjuvant therapy in stage III females, the time from diagnosis to treatment initiation (P = .013) and time to complete the planned cycles (P < .001) increased over time. Fifty-sex percent of stage IV patients were untreated. Females aged ≥70 years were less likely to receive treatment. ConclusionsSurvival estimates were lower than those reported in high-income countries. Most females were diagnosed with advanced disease, and the OS for stage III females worsened over time. Our outcomes show difficulties in delivering timely neoadjuvant therapy in an overwhelmed healthcare system. Public health authorities should improve screening practices, develop regional clinical guidelines, and expand trial enrollment.

Stereotactic ablative radiotherapy with nivolumab for early-stage operable non-small cell lung cancer: A phase 2 study.

8554 Background: Surgery is standard of care for patients with stage I non-small cell lung cancer (NSCLC). However, 5-year mortality can reach up to 30%. For patients with contraindication to surgery, treatment with stereotactic ablative radiotherapy (SABR) leads to adequate local tumor control, but has a high rate of regional and distant failure. SABR as neoadjuvant therapy for stage I NSCLC produced a pathologic complete response (pCR) rate of only 60% when surgery was performed after 10 weeks of treatment, demanding improvement in the management of both operable and inoperable early-stage NSCLC. Immune checkpoint inhibitors (ICI) are routinely used in stages III-IV NSCLC, with recent approvals in the peri-operative setting, and may be synergistic with radiotherapy. We hypothesized that neoadjuvant nivolumab plus SABR may improve pCR rate and provide insight to its changes in the tumor microenvironment. Methods: This is a phase 2, single arm, open label study evaluating neoadjuvant treatment for patients with NSCLC of up to 4 cm, with no lymph node involvement (AJCC 8th edition: up to cT2aN0), and adequate surgical conditions. Treatment consisted of nivolumab 360 mg every 3 weeks for 3 doses or unacceptable toxicity. SABR started on D1 of nivolumab, with a duration of 2 to 3 weeks, depending on the lesion size and location (3 x 18 Gy; or 5 x 10 Gy; or 8 x 7.5 Gy). Standard-of-care surgery was performed at 10 (+- 2) weeks after the last radiotherapy dose. The primary endpoint of the study is pCR rate at surgery. Tissue, blood, and stool samples were collected during treatment. Results: We included 25 patients. All but one were cared for in the Brazilian public system. Mean age was 68 years. Mean tumor size was 2.45 cm. Only 3 patients were never-smokers. Surgery was performed as scheduled in all but one patient. pCR rate was 80% (19/24) and MPR rate was 83% (20/24) of patients who underwent surgery. Twenty-nine treatment-emergent adverse events occurred in 13 patients (23 grade 1-2 events, two grade 3 and two grade 5 events, being only one grade 3 diarrhea related to experimental treatment). The single patient who was not operated died during study treatment from relapsed acute alcoholic hepatitis. The other grade 5 event was due to a respiratory infection, both unrelated to treatment. Two patients died from surgical complications 185 and 72 days after surgery, respectively (one with pulmonary artery lesion with subsequent clinical complications and other with thromboembolic events), deemed unrelated to experimental treatment. During follow-up, two additional patients died due to comorbidities, and none relapsed to date. Conclusions: In this trial with patients with significant comorbidities and smoking history from the public system in Brazil, we demonstrated a pCR rate of 80% with SABR + nivolumab. Further studies are warranted to evaluate this strategy versus surgery in operable patients with stage I disease. Clinical trial information: NCT04271384 .

Propensity-score matched analysis of the pathologic outcomes and survival benefits of neoadjuvant therapy in stage II-III anal adenocarcinoma.

Anal adenocarcinomas are a rare condition which account for less than 10% of anal cancers. The present study aimed to assess the impact of neoadjuvant therapy on the clinical and pathologic outcomes and overall survival (OS) of patients with stage II-III anal adenocarcinomas after abdominoperineal resection (APR). A retrospective cohort study of patients with anal adenocarcinoma in the US National Cancer Database (NCDB) (2010-2020) was conducted. Propensity-score matching was used to compare patients who received neoadjuvant therapy (neoadjuvant therapy group) to the no-neoadjuvant group. The primary outcome was 5-year OS whereas secondary outcomes included conversion to open surgery, hospital stay, surgical margins, 30-day mortality, 90-day mortality, and 30-day readmission. A total of 742 patients (56% male) with a mean age of 63.6 ± 12.4 years were included. A total of 214 patients in the neoadjuvant group were matched with 107 in the no-neoadjuvant group. The mean OS was similar between the two groups (47.5 vs. 44.8 months, p = 0.253). Patients who received neoadjuvant therapy had a longer median time between diagnosis and surgery (151 vs. 54 days, p < 0.001), lower 90-day mortality (1.9% vs. 6.7%, p = 0.046), more pT0 tumors (15.7% vs. 0%), less pT3-4 tumors (28.4% vs. 36.4%, p = 0.001), less pN1-2 tumors (22.9% vs. 34.7%, p < 0.001), and less lymphovascular invasion (16.2% vs. 40%, p < 0.001) than the no-neoadjuvant group. Both groups had similar conversion rates, hospital stay, 30-day mortality, 30-day readmission, and positive surgical margins. Neoadjuvant therapy before APR was associated with significant downstaging of anal adenocarcinomas and lower 90-day mortality, yet similar OS to patients who were surgically treated without neoadjuvant treatment.

Abstract P4-07-14: Long-term Outcomes After 1 or 2-3 Lines of Neoadjuvant Therapy in Stage III Inflammatory Breast Cancer

Abstract Background: Inflammatory breast cancer (IBC) is associated with a poor prognosis. While many stage III IBC patients (pts) experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to permit subsequent surgical therapy, the prognostic significance of requiring additional NAC to enable resectability is unknown. We sought to describe the pathologic complete response (pCR) rates, breast cancer-free survival (BCFS) and overall survival (OS) among pts requiring 1 vs &amp;gt;1 lines of NAC prior to surgery. Methods: Upon IRB approval, pts with stage III IBC from 2 academic institutions (Dana-Farber Cancer Institute and MD Anderson Cancer Center) who received 1L or 2-3 lines (2-3L) of NAC prior to surgery were identified. Standard NAC regimens containing different drugs, such as AC-T or TCHP, were considered as 1L. Pts with locoregional progression or metastatic disease prior to surgery were excluded. Hormone receptor (HR), HER2 status, grade, and pCR, defined as no residual invasive cancer in the breast and the axilla, were evaluated. BCFS, defined as time from surgery to locoregional and/or distant recurrence, and OS, defined as time from surgery to death, were evaluated by the Kaplan-Meier method. Multivariable Cox models stratified by institution and containing the covariates pCR and tumor subtype were utilized to estimate the HR of 2-3L vs. 1L of therapy. Results: 808 eligible pts diagnosed between 1997 and 2020 were identified. 733 (91%) had 1L and 75 (9%) had 2-3L of NAC, and the median age was 50 years. 295 (37%) had HER2+, 282 (35%) HR+HER2-, 211 (26%) had HR-HER2- disease and for 20 (2%) pts, the receptor status was unknown. The median time from diagnosis to surgery was 6 months. Grade III disease, triple-negative and HER2-positive disease were more prevalent in pts receiving 2-3L of therapy (table). pCR was achieved in 178 (24%) pts receiving 1L of NAC, and in 14 (19%) pts receiving 2-3L of NAC. At 68 months of median follow-up, 417 (52%) pts experienced a recurrence with 376 in the 1L group and 41 in the 2-3L group. The 5-year BCFS was shorter for the 2-3L group compared to the 1L group (33% v 46%, HR=1.37; 95% CI:0.99-1.91). However, in 192 pts with a pCR, BCFS was similar, regardless of the number of NAC lines. There were 38 recurrences among 178 1L pts, and 3 recurrences among 14 2-3L pts, resulting in BCFS of 76% and 83% in 1L and 2-3L pts, respectively. Overall, there were 308 deaths, 276 deaths among 1L pts and 32 among 2-3L pts. The 5-yr OS estimate in 1L versus 2-3L pts was 60% versus 53% (HR=1.32, 95% CI: 0.91-1.93). Conclusion: Among pts with stage III IBC, pCR was observed among 24% who had 1L and 19% of pts who required 2-3L of NAC. BCFS and OS were comparable among pts with pCR after 1L and 2-3L. Our results suggest the need to continue to optimize current treatment strategies in IBC to improve pCR rates across all disease subtypes regardless of the number of lines of NAC required. Citation Format: Faina Nakhlis, Samuel Niman, Naoto T. Ueno, Elizabeth Troll, Sean Ryan, Eren Yeh, Laura Warren, Jennifer Bellon, Beth Harrison, Toshiaki Iwase, H. T. Carisa Le-Petross, Sadia Saleem, Mediget Teshome, Gary J. Whitman, Wendy Woodward, Beth Overmoyer, Sara Tolaney, Meredith Regan, Filipa Lynce, Rachel M. Layman. Long-term Outcomes After 1 or 2-3 Lines of Neoadjuvant Therapy in Stage III Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-14.

792MO Neoadjuvant pepinemab in combination with nivolumab and/or ipilimumab in resectable stage III melanoma

SEMA4D has broad immunomodulatory effects in the tumor microenvironment; blocking SEMA4D in combination with checkpoint inhibitors (CI) promotes immune infiltration, enhances T cell activity, and promotes tumor regression. We hypothesized that the combination of pepinemab (pepi), which targets SEMA4D, and CI will increase immunomodulatory effects and augment response to neoadjuvant therapy in stage III melanoma.

Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.

516 Background: The incidence of triple negative breast cancer (TNBC) is higher among Black or African American (AA) women, yet AA patients (pts) are underrepresented in clinical trials, exemplifying racial disparity in oncology. We conducted a phase I/II trial to assess the safety and efficacy of durvalumab concurrent with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) neoadjuvant therapy for stage I-III TNBC. The primary efficacy endpoint was pathologic complete response (pCR; ypT0/is,N0) rate. Given the unclear efficacy and safety of immunotherapy in AA pts with breast cancer, we extended our accrual to recruit AA pts, with the goal of evaluating the association between racial groups and PD-L1 expression, stromal tumor infiltrating lymphocytes (sTILs), toxicities, treatment response and survival. Methods: Our study population included 67 pts. PD-L1 immunohistochemistry results and sTIL counts were available on 59 and 60 pts, respectively. Chi-Squared test was used to evaluate associations between race and baseline characteristics. Cox proportional hazards model was used to assess association between AA race and overall survival (OS) and event free survival (EFS), adjusting for age, comorbidities and pCR status. Multivariate logistic regression analyses were used to evaluate the association between race and pCR, development of immune-related adverse events (irAEs) and breast cancer recurrence. Results: Twenty-one pts (31%) self-identified as AA. No significant associations between AA race and baseline body mass index (BMI; p=0.075), Charlson comorbidity index (p=0.32), tumor stage (p=0.40), grade (p=0.54), PD-L1 status (0.92) and sTIL count (p=0.57) were observed. pCR rates did not significantly differ between AA and non-AA pts: 9/21 (43%) AA vs. 22/48 (48%) non-AA (p=0.71). 3-yr OS was 87% in the non-AA versus 81% in the AA cohort (HR 1.72, 95% CI 0.481-6.136; p=0.405); 3 yr EFS were 78.3% and 71.4% in non-AA and AA pts respectively. (HR 1.451, 95% CI 0.524-4.017; p=0.474). Pts with pCR were more likely to remain event-free at 3 yrs, irrespective of race (HR 0.234, 95% CI 0.066-0.829; p=0.024). In multivariate logistic regression analyses, lack of pathologic response (OR for pCR 0.17, 95% CI 0.03-0.7; p=0.02) and node positive status (OR 4.13, 95% CI 1.05-19.88; p=0.05) were associated with recurrence. The incidence of irAEs was similar between AA and non-AA pts and no significant associations were found between irAEs and pathologic response. Conclusions: pCR rates after neoadjuvant immunotherapy and chemotherapy were similar in AA and non-AA pts. Stromal TILs, PD-L1 status, 3yr OS and EFS, and the frequency of irAEs were also similar. These results suggest that when patients receive identical treatment and are monitored closely, disparities in outcomes can be mitigated or abolished. Clinical trial information: NCT02489448.

Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY’s prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.

Neoadjuvant Therapy in Stage II/III Rectal Cancer: A Retrospective Study in a Disparate Population and the Effect on Survival.

Kentucky has one of the highest rectal cancer incidences in the United States. High poverty rates have led to poor insurance coverage and inadequate access to care. The treatment of locally advanced rectal cancer utilizes a multimodal regimen requiring regular access to expert care. The rate of receipt of neoadjuvant therapy in Kentucky is unknown. This study aimed to evaluate the rate and factors associated with the receipt of neoadjuvant therapy for localized advanced rectal cancer in Kentucky and the effect on overall survival. This is a retrospective database review. This study was conducted by utilizing the Kentucky Cancer Registry at an academic center. All patients diagnosed with stage II/III rectal adenocarcinoma from 2005 to 2015 in the Commonwealth of Kentucky were included. The primary outcomes measured were the factors associated with nonreceipt of neoadjuvant therapy and overall survival. Of 1896 patients, only 46.8% received neoadjuvant therapy. Factors associated with not receiving neoadjuvant therapy included older age, female sex, low education level, high poverty level, and treatment at nonacademic centers. Survival analysis demonstrated significantly improved survival in patients receiving neoadjuvant therapy compared with other treatment regimens. This study was limited by the retrospective nature of the review and by unmeasured confounders. Our study was the first to evaluate the factors behind the low rates of neoadjuvant therapy for locally advanced rectal cancer in Kentucky. Neoadjuvant therapy in this population is beneficial for survival; efforts should be made in policy and education with focus on older patients, female patients, and treatment at nonacademic centers. Centralization of rectal cancer care improves outcomes, but we must be aware of the effect it may have on disparate populations with poor access. See Video Abstract at http://links.lww.com/DCR/B596. ANTECEDENTES:El estado de Kentucky tiene una de las mayores incidencias de cáncer de recto en los EE. UU. Debido a una alta tasa de pobreza, el porcentaje de la población que cuenta con seguro de salud, es muy limitado, y por lo tanto el acceso a una atención de alto nivel es muy bajo. El tratamiento del cáncer de recto localmente avanzado, es multidisciplinario, lo que exige acceso y disponibilidad a un grupo experto. Se desconoce la tasa de pacientes que reciben terapia neoadyuvante en Kentucky.OBJETIVO:Establecer la tasa y los factores asociados con el uso de terapia neoadyuvante en el tratamiento del cáncer de recto localmente avanzado en Kentucky, y su efecto en la supervivencia global.DISEÑO:Revisión retrospectiva de una base de datos.ESCENARIO:Este estudio se llevó a cabo utilizando el Registro de Cáncer de Kentucky en un centro académico.PACIENTES:Se incluyen todos los pacientes diagnosticados con adenocarcinoma de recto, de la Mancomunidad (Commonwealth) de Kentucky, en estadio II / III entre 2005 y 2015.PRINCIPALES MEDIDAS DE RESULTADO:Establecer los factores asociados con el hecho de no recibir terapia neoadyuvante; y establecer la supervivencia global.RESULTADOS:De 1896 pacientes evaluados, solo el 46,8% recibió terapia neoadyuvante. Los factores asociados, para no haber recibido terapia neoadyuvante fueron: la edad avanzada, sexo femenino, bajo nivel educativo, alto nivel de pobreza y tratamiento en centros no académicos. El análisis de la supervivencia mostró una supervivencia significativamente mejor en los pacientes que recibieron terapia neoadyuvante en comparación con otros esquemas de tratamiento.LIMITACIONES:Revisión retrospectiva, factores de confusión no medidos.CONCLUSIONES:Nuestro estudio ha sido el primero en evaluar los factores determinantes de las bajas tasas de terapia neoadyuvante para el tratamiento del cáncer de recto localmente avanzado en Kentucky. La terapia neoadyuvante mejora y favorece la supervivencia en esta población, por lo tanto se deben hacer esfuerzos en las políticas de salud, así como en educación, enfocados a los pacientes mayores, pacientes femeninas y tratamiento en centros no académicos. El centralizar la atención del cáncer de recto, mejora los resultados, pero debemos ser conscientes del efecto que puede tener en poblaciones desiguales económicamente, con acceso deficiente a la posibilidad de recibir atención de alto nivel. Consulte Video Resumen en http://links.lww.com/DCR/B596.

Pegylated liposomal doxorubicin as neoadjuvant therapy for stage II–III locally advanced breast cancer

Conventional anthracyclines represent a cornerstone drug in the treatment of breast cancer. Pegylated liposomal doxorubicin (PLD) has similar efficacy to anthracyclines with reduced toxicity. This study was to compare the efficacy and safety of PLD-based neoadjuvant chemotherapy (NAC) with epirubicin-based treatment for breast cancer. 81 breast cancer patients were enrolled in this retrospective study. The objective response rate (ORR) in the PLD group was 74.1%, the 3-year disease-free survival(DFS) and overall survival(OS) were 81.5% and 88.9%. The PLD group achieved similar efficacy to the EPI group. The PLD group showed a low rate of neutropenia , nausea and vomiting, but a higher rate of mucositis and hand-foot syndrome. In neoadjuvant chemotherapy for invasive breast cancer, PLD provides comparable efficacy to epirubicin with a safe cardiac toxicity profile and manageable adverse effects.

Factors Associated With Survival in Complete Pathologic Response Non–Small Cell Lung Cancer

ObjectivesThere is a strong association with improved survival for patients with non–small cell lung cancer (NSCLC) who have developed a pathological complete response (pCR) after neoadjuvant therapy. A national database was used to investigate factors associated with long-term survival in this cohort of patients. PatientsRetrospective review was completed of the National Cancer Database of patients who obtained pCR and had neoadjuvant therapy for stage I to stage III NSCLC between 2004 and 2014. All patients had neoadjuvant chemotherapy with or without radiation therapy. MethodsUnivariate and multivariable analysis was performed on factors associated with overall survival (OS), including gender, clinical stage, and nodal count. Patients were divided into 2 groups based on the Commission on Cancer–recommended median number of lymph nodes (LNs) examined: 0 to 9 LNs and ≥10 LNs. Chi-square and Wilcoxon rank-sum tests were used to compare patient, hospital, and clinical variables between groups. ResultsIncreased age (hazard ratio [HR] 1.02, 95% confidence interval [CI], 1.00-1.03), neoadjuvant radiation therapy (HR 1.48, 95% CI, 1.10-2.00), and pneumonectomy (HR 1.64, 95% CI, 1.22-2.22) were associated with worse survival in the 759-patient cohort. Multivariable regression demonstrated having ≥10 nodes harvested (HR 0.71, 95% CI, 0.56-0.89) was associated with improved survival as was every increase in LN harvest up to 17 LNs. No significant differences in 5-year OS were found between clinical stage I, II, and III, respectively (66.1% vs. 60.9% vs. 58.6%, P = .288). ConclusionThis study shows that younger age, increasing LN harvest, female sex, the absence of neoadjuvant radiation therapy and non-pneumonectomy resections are all associated with improved OS in patients with NSCLC who have developed pCR.

Uptake and disparities of neoadjuvant therapy for stage III non-small cell lung cancer.

6571 Background: The optimal use and sequence of radiation therapy (RT), chemotherapy, and surgery for patients with stage III non-small cell lung cancer (NSCLC) is unknown. We conducted a cross-sectional study using the Surveillance Epidemiology and End Results (SEER) population-based cancer registry to examine the relationship between year of diagnosis and receipt of neoadjuvant RT for patients with stage III NSCLC diagnosed in the United States from 2000 to 2008, with additional focus on the role of race and treatment location. Methods: Thirteen SEER registries were used for data analysis. Patients diagnosed with stage III NSCLC treated with both surgery and RT between the years 2000 and 2008 were included. We used multiple logistic regression to describe the relationship between type of therapy for lung cancer and year of diagnosis. Covariates identified for analysis included age, grade, sex, race, ethnicity, and SEER registry. Results: The total sample size was 393,711 of which 5,949 patients met our inclusion criteria. The cohort had a mean age of 64, was predominantly white (85.8%) and had predominantly high grade tumors (50.9%). Use of neoadjuvant RT for stage III NSCLC was lowest in 2000 and higher in every year from 2002 to 2008 (OR 1.325 in 2002, p= 0.035; 1.921 in 2007, p&lt;0.0001). Substantial heterogeneity among registries existed, with more neoadjuvant RT use in Seattle and San Francisco-Oakland (OR 1.83, 1.698 p&lt;0.0001 and 0.0002 respectively) and less use in Metropolitan Detroit, New Jersey and Louisiana (OR 0.754, 0.570, 0.493, p=0.25, &lt;0.0001, and &lt;0.0001 respectively). Black race was significantly associated with lack of neoadjuvant therapy without controlling for registry, but the association weakened after controlling for registry (OR 0.81, p=0.072). Conclusions: The use of neoadjuvant RT for stage III NSCLC substantially increased from 2000 to 2008. Location of treatment was strongly associated with receipt of neoadjuvant therapy and outweighed the association of race and therapy. The effort to equitably distribute care should focus additional study on the important role of regional and local medical culture in determination of medical care.

Abstract OT1-1-09: Opti-HER HEART: A prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients with operable HER2-positive breast cancer.

Abstract Background: In recent years, the concomitant use of two anti-HER2 therapies has been generating great expectations. Of note, despite the high activity reported by several studies, none has ever included a chemotherapeutic regimen with anthracyclines. The therapeutic value of anthracyclines in HER2-positive breast cancer (BC) has been well established. However, the feasibility of their combination with trastuzumab is still controversial. Liposomal anthracyclines, on the other hand, may offer a safer alternative. Of note, in our institutional experience using a regimen of liposomal doxorubicin plus weekly paclitaxel and trastuzumab as standard neoadjuvant therapy for stage II-III breast cancer (BC) patients reach a pathological complete response (pCR) rate of 65%, without any grade 3/4 cardiac toxicity. Trial Design: This study seeks to optimize the treatment of patients with operable HER2-positive BC, while minimizing cardiac risk, by combining dual anti-HER2 blockade plus a taxane and a liposomal anthracycline. In this single-arm, phase II clinical trial, patients will receive neoadjuvant therapy for six 21-day cycles. Regimen consists of: trastuzumab 4 mg/kg loading dose on Day 1 of Cycle 1, then 2 mg/kg on Days 8 and 15 and on Days 1, 8, and 15 of subsequent cycles; pertuzumab 840 mg loading dose on Day 1 of Cycle 1, then 420 mg on Day 1 of the following cycles; liposome-encapsulated doxorubicin 50 mg/m2 on Day 1 of each cycle; and, paclitaxel 80 mg/m2 on Days 1, 8, and 15 of each cycle. ECG will be performed at baseline and every planned visit. Left ventricular ejection fraction (LVEF) decline will be assessed at baseline, weeks 6 and 12, before surgery, and every 3 months thereafter during the adjuvant period, for a total of 12 months. In order to assess biomarkers of cardiac injury, blood samples will be collected at the same time points. An initial safety run-in phase is included, in which the first ten enrolled patients undergo an intensified safety monitoring for cardiac and hematological adverse events. Eligibility: Female patients 18–74 years old with primary HER2-positive invasive breast cancer eligible for definitive surgery, with adequate cardiac function. Specific aims: The primary objective is to assess cardiac safety, measured by the incidence of symptomatic cardiac events and by asymptomatic LVEF decline. Secondary objectives include efficacy, breast conservation rate, additional safety and tolerability, and predictive biomarkers of cardiotoxicity. Statistical methods: Assuming that the incidences of cardiac events with regimens containing anti-HER2 agents are 3% for symptomatic and 15% for asymptomatic, 83 patients will be required to reject the null hypothesis with 80% confidence. Additionally, efficacy will be evaluated by pCR rates. Target accrual: Recruitment started in September 2012 and will include 83 patients across 20 sites in Spain. Trastuzumab and pertuzumab are kindly provided by Roche. The trial is supported by a grant from TEVA. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-09.

Outcomes Assessment of the Surgical Management of Esophageal Cancer in Younger and Older Patients

The aim of this study was to assess the influence of age on disease presentation, clinical and pathologic staging, postoperative outcomes, costs, and long-term survival after esophagectomy for esophageal malignancy. All patients undergoing esophagectomy for cancer between 1991 and 2011 were prospectively enrolled in an Institutional Review Board approved database. A total of 493 patients underwent surgical resection during the study period; 58 (11.76%) of these patients were 50 years or less (44 ± 4.7) and 435 patients were greater than 50 years (67 ± 8.44). There was no difference in clinical stage; however, patients 50 years or less were more likely to have adenocarcinoma and reduced Charlson comorbidity index and younger patients tended to have a more delayed presentation as manifested by an increased period of dysphagia and a greater degree of weight loss. In the 50 or less age group there was a significantly greater use of neoadjuvant therapy in stage II patients and the use of neoadjuvant chemotherapy significantly decreased with increasing age. Surgery in the 50 or less age group was associated with significantly reduced intensive care unit stay, incidence of postoperative complications, and overall costs. Multivariate analysis also confirmed associations between increasing age and increased incidence of postoperative complications and cost. There were no significant differences in pathologic stage, positive resection margins, incidence of complete response to neoadjuvant therapy, or in overall survival. This study demonstrates younger patients have fewer complications and lower overall treatment costs after esophagectomy. In spite of having a more delayed presentation, younger patients presented with a similar stage and demonstrated similar overall survival.

A Neoadjuvant Biochemotherapy Approach to Stage III Melanoma: Analysis of Surgical Outcomes

Completion lymph node dissection (CLND) and adjuvant therapy are recommended for node-positive melanoma patients. We sought to analyze our institution's experience with neoadjuvant biochemotherapy in stage III patients. Clinical information was extracted from a retrospective database on stage III melanoma patients. Eligible patients received two cycles of biochemotherapy prior to their CLND. There were 153 patients available for analysis. The average tumor depth was 2.5 mm. More than half of all patients presented with sentinel lymph node-positive disease. Surgical complications occurred in 23% of patients. Patients who experienced an adverse event during their neoadjuvant therapy had a worse overall survival when compared with those who did not (p = 0.005). Our data suggest that aggressive neoadjuvant treatment prior to CLND does not impact surgical complications. Our surgical outcomes are similar to the current literature when adjuvant therapy is used in stage III melanoma. The inability to tolerate neoadjuvant therapy in stage III melanoma is a negative prognostic indicator.

Assimilation of evidence-based medicine into clinical practice: Adjuvant radiotherapy in the multidisciplinary treatment of rectal cancer.

552 Background: Implementation of evidence based standards is recognized to be problematic. Level 1 evidence supports the superiority of neoadjuvant therapy for stage II/III rectal cancer. The purpose of this study was to determine to what extent evidence based medicine has impacted clinical practice. Methods: Stage II/III rectal cancer patients undergoing surgery from 1998-2007 were identified in the SEER tumor registry using SEER*Stat 6.2. Variables were extracted and analyzed in SPSS; trends were evaluated with regression models and survival with log rank test. Results: A total of 25,129 patients were identified, 15,769 (63%) were treated with adjuvant radiotherapy. A majority were &gt; 60 years old (56%), white (82.8%), male (60.9%), had stage III cancers (59.2%) and treated with neoadjuvant radiotherapy (54.5%). Significant changes in timing of adjuvant radiotherapy were noted over the study period. In 1998 28.1% of patients were treated neoadjuvantly, this increased to 74% in 2007, a 263% increase. Scatter plot best fit lines intersect in approximately year 2002, p value of trend &lt;0.001. On univarate analysis race (p=0.018), sex (p&lt;0.001), year of diagnosis (p&lt;0.001), age (p&lt;0.001), and stage (p&lt;0.001) were associated increased likelihood of neoadjuvant radiotherapy. Logistic regression found male sex (OR 1.14, p&lt;0.001), year (OR 1.223, p&lt;0.001) and stage II (OR 1.39, p&lt;0.001) were predictors of neoadjuvant therapy. Significant increases in preoperative radiotherapy were observed for all races and cancer stages (p&lt;0.001). There was a significant survival advantage for those treated with adjuvant radiotherapy, median survival 39 vs. 93 months p&lt;0.0001. There, however, was no survival advantage to neoadjuvant vs. postoperative radiotherapy, median survival 94 vs. 93 months, p=0.749. Conclusions: When adjuvant radiotherapy is utilized, there has been rapid adoption of evidence based standards for Stage II/III rectal cancer. However, substantial numbers of patients are not receiving care recognized to improve outcomes.

Room for improvement? The adoption of multimodal esophageal cancer care in the United States.

78 Background: Consensus guidelines recommend neoadjuvant chemo- or chemoradiation therapy as the preferred treatment for locally advanced esophageal adenocarcinoma; however, it is unknown if this recommendation has been widely adopted in the U.S. Our objective was to examine esophageal cancer multimodal therapy and identify factors associated with the use of neoadjuvant therapy. Methods: From the National Cancer Data Base, patients with middle third, lower third and GE junction (GEJ) adenocarcinomas were identified. Patients who were clinical stage I-III and underwent surgical resection were included. Separate logistic regression models were developed to identify predictors of neoadjuvant therapy utilization and outcomes. Results: From 1998 to 2007, 8,051 patients underwent surgical resection for esophageal cancer: 16.3% stage I, 45.0% stage II and 38.7% stage III. For stage II/III tumors, neoadjuvant use increased (49.0% to 77.8%, p&lt;0.001). After adjustment, factors associated with underuse of neoadjuvant therapy in stage II/III patients were older age, Black or Hispanic ethnicity, more severe comorbidities, tumor location (GEJ and middle vs. lower third), tumor size ≥ 2cm, stage II (vs. III) and geographic region. Stage II/III patients not receiving neoadjuvant had an over two fold increased risk of positive lymph nodes (OR 2.14. 95% CI 1.79 – 2.55, p&lt;0.001). In addition, the positive surgical margin rate increased almost three fold (OR 2.80 95% CI 2.17-3.62, p&lt;0.001) but 30-day postoperative mortality risk was not significantly affected (OR 1.50 95% CI 0.94-2.39; p=0.090). For stage I patients, neoadjuvant therapy decreased over time (38.0% to 11.4%, p&lt;0.001). The overuse of neoadjuvant therapy was associated with higher tumor grade, larger tumor size, and low surgical case volume (all p&lt;0.05). Conclusions: The adoption of neoadjuvant therapy has increased in the past decade; however, opportunity exists to improve guideline treatment for locally advanced esophageal cancer. Registry-based feedback to individual hospitals, such as benchmark comparison tools, could help institutions provide care in concordance with national guidelines. No significant financial relationships to disclose.

Neoadjuvant therapy for stage II-III breast cancer with weekly nab-paclitaxel, every-three-week carboplatin, and targeted agents: Interim dose delivery and toxicity data.

e11010 Background: To evaluate the efficacy and safety of neoadjuvant weekly (w) nanoparticle albumin-bound paclitaxel (Abraxane, NP) and every-3-week (q3wk) carboplatin (Cb) with either bevacizuma...

Analysis of prognostic factors for surgery after neo-adjuvant therapy for stage III non-small cell lung cancer

In order to explore the possibility to predict the risk factors for postoperative complications and survival time, the clinical data of 152 patients (including 116 males and 36 females) who had undergone neo-adjuvant therapy and surgery for stage IIIA and B non-small cell lung cancer (NSCLC) were retrospectively analyzed. Demographic data, preoperative functional parameters, staging, induction regimen (chemotherapy alone or associated with radiotherapy), associated disorders, and data about operation were collected. Chi-square test and multivariate analysis fitting the unconditional logistic regression model were performed to identify predictors of postoperative complications, while Kaplan-Meier and multivariate Cox proportional hazard model were employed to identify predictors of survival time, respectively. The univariate analysis demonstrated that forced expiratory volume in 1 second predicted percent (FEV1%, P=0.040) and associated disorders (P=0.020) were the predictive factors of complications, but multivariate analysis found no independence factors (P>0.05) of it. Univariate Kaplan-Meier analysis showed that stage (P=0.050) and pneumonectomy (P=0.018) affected the survival time. However, multivariate Cox proportional hazard model analysis demonstrated that only pneumonectomy (P=0.026) was associated with a decreased survival time, but no differences between right and left pneumonectomy were found. The results suggest that the risk factor for postoperative complications is acceptable, and pneumonectomy is associated with increased mortality, which should be performed only in stage III NSCLC patients.

A phase II study of neoadjuvant docetaxel plus doxorubicin (KBCS-01) in stage II, III breast cancer

This multicenter phase II study was conducted to evaluate the response and safety of a combination of docetaxel plus doxorubicin as neoadjuvant therapy for stage II, III breast cancer. Patients with stage II or III breast cancer underwent three cycles of neoadjuvant chemotherapy with doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 every 3 weeks followed by curative surgery. Prophylactic GCSF was not used. Ninety patients were enrolled in the study and 86 were evaluable for efficacy. The median age was 43 years (range, 30-69). The mean relative dose intensity was 0.98 for docetaxel and 0.98 for doxorubicin. Breast-conserving surgery was performed in 12 (13.7%) patients. The clinical overall response rate was 86% and pathologic complete response was 10.5%. Grade 3/4 neutropenia was observed in 26% of total 258 cycles and febrile neutropenia was observed in 15.8%. Pneumonia was observed in one patient and grade 3 mucositis was observed in three patients. Docetaxel and doxorubicin was an effective and well-tolerated neoadjuvant chemotherapy for stage II and III breast cancer. Clinical benefit of this treatment will be confirmed by survival data with long term follow up.