Adjuvant Treatment Outcomes Research Articles

Therapeutic Outcomes in 691 Angiosarcomas of the Head and Neck-A Retrospective SEER Study.

Angiosarcomas (AS) are an aggressive subtype of head and neck tumors. Current outcome research is limited to single-surgeon and/or single-institution data. This study analyzes the Surveillance, Epidemiology, and End Results program (SEER) database data to improve outcomes of head and neck AS. In this study, the authors accessed the SEER database from 2000 to 2020 to identify patients who underwent surgical and/or nonsurgical treatment of head and neck AS. Data included demographics, diagnostic workup, tumor characteristics, treatment pathways, and therapy outcomes. The study included 691 patients (210 females, 481 males) with AS of the head and neck. The median tumor size was 40mm. Most patients (63%) underwent surgery, with surgery followed by radiation being the most common treatment combination (50%). Median survival was 16 months. Patients treated with surgery showed significantly longer survival (18mo) compared with nonsurgery cases (12mo, P<0.001). Neoadjuvant treatment significantly improved survival (28mo) compared with non-neoadjuvant cases (15mo, P=0.023). Adjuvant treatment also improved overall survival (19mo) versus nonadjuvant treatment (14mo, P<0.001). There was no significant difference between neoadjuvant and adjuvant treatment outcomes (P=0.270). Bottom of Form This study compares the outcomes of multimodal treatments, especially surgery and radiotherapy, for head and neck AS, emphasizing tailored approaches to optimize patient outcomes and extend survival. Future research should refine these strategies.

Survival outcomes of adjuvant treatment in upstaged clinical T2N0 rectal cancer: are we underutilizing therapy?

BackgroundPatients with rectal cancer staged as clinical T2N0 (cT2N0) are recommended to undergo upfront resection. However, when the tumor is subsequently upstaged to pathologic T3N0 (pT3N0), there are no clear guidelines for adjuvant treatment. This study aimed to analyze national trends in adjuvant management and to identify differences in morbidity or survival. MethodsUsing the National Cancer Database (2004–2020), adult patients with cT2N0 rectal adenocarcinoma that were upstaged to pT3N0 after resection were identified. The treatment groups included (i) surgery alone, (ii) surgery + postoperative (post-op) chemotherapy alone, (iii) surgery + post-op chemoradiation (CRT), and (iv) surgery + chemotherapy + CRT. Cox proportional hazard models and Kaplan-Meier curves (6-month landmark analysis) were used to compare survival outcomes. ResultsThe analytic cohort included 800 patients who received the following treatments: surgery alone (496 [60%]), surgery + post-op chemotherapy (139 [17%]), surgery + post-op CRT (137 [15%]), and surgery + chemotherapy + CRT (69 [8%]). Patients who underwent post-op chemotherapy or chemotherapy + CRT had higher rates of poor/undifferentiated tumors (15.7% and 15.4%, respectively) than those who underwent surgery alone (8.8%) (P = .047). Over the study period, surgery alone decreased from 86.7% to 65.6%, with concomitant increases in post-op adjuvant therapy. Post-op chemotherapy (hazard ratio [HR], 0.336; 95% CI, 0.196–0.575) and chemotherapy + CRT (HR, 0.447; 95% CI, 0.231–0.866) remained independently associated with improved overall survival. Of note, 5-year survival was the lowest in the surgery-alone group (62.5%). ConclusionPost-op adjuvant regimens, including chemotherapy, were independently associated with improved survival in patients with cT2N0 rectal cancer upstaged to pT3N0. Adjuvant therapy may be underutilized in this setting.

PLK3 amplification and tumor immune microenvironment of metastatic tumors are linked to adjuvant treatment outcomes in uterine serous cancer.

Uterine serous carcinoma (USC), an aggressive variant of endometrial cancer representing approximately 10% of endometrial cancer diagnoses, accounts for ∼39% of endometrial cancer-related deaths. We examined the role of genomic alterations in advanced-stage USC associated with outcome using paired primary-metastatic tumors (n = 29) treated with adjuvant platinum and taxane chemotherapy. Comparative genomic analysis of paired primary-metastatic patient tumors included whole exome sequencing and targeted gene expression. Both PLK3 amplification and the tumor immune microenvironment (TIME) in metastatic tumors were linked to time-to-recurrence (TTR) risk without any such association observed with primary tumors. TP53 loss was significantly more frequent in metastatic tumors of platinum-resistant versus platinum-sensitive patients and was also associated with increased recurrence and mortality risk. Increased levels of chr1 breakpoints in USC metastatic versus primary tumors co-occur with PLK3 amplification. PLK3 and the TIME are potential targets for improving outcomes in USC adjuvant therapy.

Defining optimal adjuvant treatment for high-risk early-stage endometrial cancer

<h3>Objectives:</h3> There is a paucity of data to determine the optimal adjuvant treatment of early-stage, high-risk endometrial histologies. While many retrospective series focus on uterine serous cancer, the optimal treament for other high risk subtypes, including G3 endometrioid cancer, clear cell carcinoma or carcinosarcoma is not yet clear. We sought to determine patterns and outcomes of adjuvant treatment for early-stage high-risk endometrial cancers of multiple histologic subtypes. <h3>Methods:</h3> After Institutional Review Board approval, a retrospective review of patients at Montefiore Medical Center diagnosed with early stage high-risk endometrial cancer between 2006 and 2018 was conducted. Inclusion criteria included: 1) Stage I-II disease 2) Grade 3 endometrioid, carcinosarcoma, clear cell, serous, or mixed histologies. Demographic and clinical information pertaining to cancer treatment was collected. The primary outcome was recurrence-free survival. Univariate and multivariate analyses were performed and a Kaplan-Meier progression free survival curve was created using STATA 14.2. P-value <0.05 was considered statistically significant. <h3>Results:</h3> A total of 1208 patients with endometrial cancer were identified, 249 of which met inclusion criteria. Sixty-percent (149) of patients had serous, clear cell, or mixed histologies, 17% (43) had carcinosarcoma, 23% (57) had Grade 3 endometrioid histology. Most patients received adjuvant combination chemoradiotherapy (52%, N=131) whereas 20% (49) received radiation alone (brachytherapy or external beam), 7% (18) received chemotherapy alone, and 20% (50) received no adjuvant treatment. Of the 48 (19%) disease recurrences, 25 (45%) were distant metastases at the time of recurrence. Combined chemoradiotherapy was associated with increased recurrence-free survival compared with chemotherapy alone (p=0.026) or radiation alone (p=0.004). Compared to G3 endometrioid histology, the hazard ratios for recurrence were: 3.70 (CI 1.31-10.41, p=0.01) for serous histology, 1.37 (CI 0.15-12.21, p=0.78) for clear cell, 9.70 (CI 3.22-29.16, p<0.01) for carcinosarcoma, and 4.59 (CI 1.28-16.46, p=0.02) for mixed histology. Charlson Cormorbidity Index was also associated with cancer recurrence (HR 1.53, CI 1.28-1.82, p<0.01), as was age (HR 0.95, CI 0.92-0.99, p=0.01). <h3>Conclusions:</h3> Multimodal treatment with chemotherapy and radiation therapy is associated with increased recurrence free survival in patients with high-risk early-stage endometrial cancers, in comparison to radiation or chemotherapy alone after surgical staging. Histologic subtype, comorbid conditions, and age all significantly impact survival. Notably, recurrence in clear cell tumors were not significantly impacted by adjuvant treatment with chemotherapy and radiation therapy. Randomized trials are needed to determine the optimal treatment of high-risk histologic subtypes.

Long term outcomes between adjuvant radiotherapy and combined radiotherapy with hormonal treatment after radical prostatectomy in high risk prostate cancer

Objective: To determine the oncological outcome of adjuvant treatment between radiotherapy (RT) alone and combined radiotherapy with androgen deprivation therapy (ADT) in high risk prostate cancer patients after radical prostatectomy (RP). Materials and Methods: All medical records of high risk-prostate cancer patients (including PSA &gt; 20 ng/ml, pT3-pT4 or Gleason score 8-10) who underwent RP in Siriraj Hospital between 2000 and 2016 were retrospectively reviewed. Demo-graphic data, pathological staging, types of adjuvant treatment, time to follow up and time to biochemical recurrence (BCR) were analyzed. Results: Undetectable PSA after RP was achieved in 1009 out of 1221 high risk prostate cancer patients who had been followed up at least 6 months after surgery. Pathological staging pT2, pT3, pT4 and N1 was 23.8%, 73%, 0.8% and 4.7%, respectively. Forty one percent received adjuvant treatment (41 adjuvant RT alone, 74 combined adjuvant RT and ADT, 303 ADT alone). Median follow up time in the adjuvant RT group and combined treatment group was 63.8 months (8.9 - 210.7). BCR rates were 22% (9 of 41) for adjuvant RT and 12.2% (9 of 74) for adjuvant combined treatment. 10-year BCR-free survival in the two groups was 70.2% and 83.8%, respectively. There was no statistical difference between adjuvant RT and adjuvant combined treatment in terms of survival benefit (Hazard Ratio 0.40; p = 0.057). Conclusion: Adjuvant radiotherapy after radical prostatectomy increases long term survival outcomes for high risk prostate cancer patients. This study shows that combined adjuvant RT and ADT may improve BCR-free survival.

Pediatric Malignant Glomus Tumor of the Cervical Paraspinal Tissue: Case Report and Review of the Literature

AbstractGlomus tumors are mesenchymal tumors that arise from glomus bodies and most frequently occur in the distal extremities. These tumors can occur throughout the body and are typically benign. However, a very small fraction of glomus tumors displays aggressive features and are considered atypical or malignant. We report on our experience and management of the first case in the literature of a malignant glomus tumor in a child originating in the paraspinal region with involvement of the cervical spine. Malignant glomus tumors tend to be locally aggressive, and en bloc resection is difficult, especially when the tumors occur in the head and neck. Additional studies on disease progression and adjuvant treatment outcomes are necessary to determine the best treatment approach and long-term outcomes in patients with malignant glomus tumors.

Predictive Value of Molecular Subtypes in Premenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the ABCSG Trial 5.

To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy. Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors. 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80-6.87; P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS). Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF.See related commentary by Hunter et al., p. 5543.

Recurrence After Surgery for Stage II Endometrial Cancer Leads to Limited Survival: Practice Patterns and Outcomes of Adjuvant Treatment in an Integrated Healthcare System

Though increased risk of locoregional recurrence in intermediate-risk endometrial cancer warrants adjuvant treatment, the type and extent of therapy for FIGO Stage II disease is not well-standardized. Here, we observe practice patterns and outcomes for such patients in our integrated healthcare system. All incident cases of endometrioid adenocarcinoma diagnosed 2010-2017 were identified by central cancer registry. Patients who underwent definitive surgery and had pathological Stage II disease (cervical stromal invasion without extrauterine involvement) were included. Clinical data were obtained by electronic medical record abstraction. Gastrointestinal (GI) and genitourinary (GU) toxicities were graded by CTCAE 5.0. Of 4317 cases identified, 119 patients were eligible for analysis. Median age at diagnosis was 61 years. Median follow-up was 50.4 months (IQR 33.4-83.7). Nodal dissection was performed in 61% of patients with 14 median nodes (range 1-45) identified. Pathological grade was 1 in 55 (46%), 2 in 48 (40%), and 3 in 16 (13%). Lymphovascular invasion was seen in 39 (33%). No adjuvant treatment was given to 27 patients (23%). Pelvic external beam radiotherapy (EBRT) alone was administered to 10 patients (8%), vaginal brachytherapy (VBT) alone to 10 (8%), and both to 72 (61%). The most common EBRT and VBT doses were 4500cGy (range 4140-5040) and 2100cGy (range 1200-2100), respectively. Adjuvant chemotherapy only was given to 7 patients (6%), and with radiation to 6 patients (5%). Late grade 2 GI or GU radiation toxicity was experienced by 4 patients (4%); 2 developed late small bowel obstruction. Recurrences were noted in 23 patients (19%): locoregional in 9, distant in 14. Of locoregional recurrences, 6 were after no radiation and 3 after EBRT; 4 failed at the cuff, 4 in the para-aortic nodes, and 1 in the pelvic nodes, leading to 3 deaths. Of distant recurrences, 5 were in the lung and 5 in the omentum. Of 16 patients with grade 3 tumors, 5 recurred distantly and all died of disease; of these, 2 received 3 and 6 cycles adjuvant chemotherapy each. Median time to death was 4.9 months (range 3.5-26.8). At time of analysis, 98 patients were alive (82%) and 21 (18%) had died, 14 of cancer-related causes. Median time from diagnosis to death overall was 27.3 months (range 6.5 – 50.5); median time from recurrence to death was 9.6 months (range 1.3 – 37.1). Most Stage II patients received adjuvant radiation and tolerated it well with few late effects. While locoregional recurrences were uncommon among those receiving radiation, any recurrence led to limited survival among the majority, particularly in those with distant recurrences. As nearly one-third of patients with grade 3 disease developed distant disease, further study is merited in this group which may benefit from systemic therapy.

Treatment options and results of adjuvant treatment in nonmuscle-invasive bladder cancer (NMIBC) during the Bacillus Calmette-Guérin shortage.

Given the worldwide shortage of Bacillus Calmette-Guérin (BCG), we review the efficacy of alternative BCG application schedules, doses or strains and intravesical chemotherapy in patients with nonmuscle-invasive bladder cancer (NMIBC). Modifying BCG schedules by reducing the dose is preferable to reducing the frequency of BCG that increases recurrence rates and should be avoided if possible. Changing the BCG substrain represents a reasonable option, as current evidence does not suggest different oncological outcomes with specific BCG substrains. Mitomycin C (MMC) alone is inferior to BCG with maintenance, but promising results have been demonstrated when used with chemohyperthermia and electromotive drug administration. Several other intravesical chemotherapies including Gemcitabine and Epirubicin should be used when both BCG and MMC are in short supply. In case of BCG shortage, much will depend on the severity and length of the BCG shortage, but our review supports several solutions: First, we recommend contacting the local pharmacist or BCG supplier to consider alternative BCG strains or sterile splitting of BCG doses. In the complete absence of BCG, consideration should be given to MMC with chemohyperthermia or electromotive drug administration where available or other intravesical chemotherapy. High-risk patients should be considered for cystectomy.

Long-term efficacy of surgical resection with or without adjuvant therapy for treatment of secondary glioblastoma in adults.

BackgroundThere are limited studies on treatment strategies and associated clinical outcomes in patients with secondary glioblastoma (sGBM). We sought to investigate the prognostic factors and treatment decisions in a retrospective cohort of patients with sGBM.MethodsOne hundred and seventy-one patients with sGBM who met the screening criteria were included in this study. Kaplan–Meier survival analysis and Cox survival analysis were used to detect prognostic factors. R (v3.5.0) and SPSS software (v25.0, IBM) were used to perform statistical analyses.ResultsThe median overall survival was 303 days (range 23–2237 days) and the median progression-free survival was 229 days (range 33–1964 days) in patients with sGBM. When assessing the relationship between adjuvant treatment outcome and extent of resection (EOR), the results showed that patients underwent gross total resection can benefit from postoperative radiotherapy and chemotherapy, but not in patients underwent subtotal resection. In addition, we also found that aggressive adjuvant therapy can significantly improve clinical outcomes of IDH1-mutated patients but no significant prognostic value for IDH1-wildtyped patients. The univariate Cox regression analyses demonstrated that EOR, adjuvant therapy, and postoperative Karnofsky Performance Scores were prognostic factors for patients with sGBM, and multivariate COX analysis confirmed that adjuvant therapy and EOR were independent prognostic factors.ConclusionsFor patients with sGBM, aggressive postoperative adjuvant therapy after gross total resection was recommended. However, we did not detect a benefit in IDH1-wildtype patients in our cohort.

Adjuvant Therapy for High-Risk Stage II or III Colon Adenocarcinoma: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study.

Purpose: To determine the optimal adjuvant chemotherapy regimen for patients with high-risk stage II or III colon adenocarcinoma, we conducted this propensity score-matched, nationwide, population-based cohort study to estimate the effects of adjuvant treatments in high-risk stage II or III colon adenocarcinoma. Patients and Methods: Using propensity score matching, we minimized the confounding effects of sex, age, pathologic stage, tumor location, total chemotherapy cycles, and Charlson comorbidity index scores on adjuvant treatment outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. We selected the patients from the Taiwan Cancer Registry database and divided them into four groups: Group 1, comprising patients who received surgery alone; group 2, comprising those who received adjuvant fluoropyrimidine alone; group 3, comprising those who received adjuvant oxaliplatin-fluoropyrimidine-leucovorin (FOLFOX); and group 4, comprising those who received adjuvant folinic acid-fluorouracil-irinotecan (FOLFIRI). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs, as well as the 95% confidence intervals (Cis)) for mortality observed for groups 1, 2, and 4 relative to group 3 were 1.55 (1.32 to 1.82), 1.22 (1.05 to 1.43), and 2.97 (2.43 to 3.63), respectively. After a stratified subgroup analysis for high-risk stage II colon adenocarcinoma, we noted that the aHR (95% CI) for mortality for group 2 relative to group 3 was 0.52 (0.30 to 0.89). Conclusions: Adjuvant fluoropyrimidine alone is the most optimal regimen for patients with high-risk stage II colon adenocarcinoma compared with the other adjuvant chemotherapy regimens. Adjuvant FOLFOX can serve as an optimal regimen for patients with pathologic stage III colon adenocarcinoma, regardless of age, sex, or tumor location.

980P - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)

BackgroundThe estimand framework requires a precise definition of the clinical question of interest (estimand) to account for “intercurrent” events, eg in RCC the appearance of second primary malignancies or the start of new therapy. Selection of the appropriate estimand will drive trial design and support discussions about relevant treatment effects, interpretation of study results, and the added value of drugs. MethodsA cross-industry collaboration of statisticians and clinicians has worked on connecting estimand framework concepts to different applications. Data from previously reported phase 3, placebo-controlled studies S-TRAC (NCT00375674) and PROTECT (NCT01235962) will be used to illustrate the effect of different estimands on adjuvant treatment outcomes in RCC. ResultsTable shows the treatment outcomes for different estimands. Treatment outcomes were similar to the specified primary analysis irrespective of the clinical question asked; however, the studies were not powered to address each of these questions and not all reached statistical significance. The new framework clarifies that different analyses address different questions. The choice of the primary estimand impacts study design and may have regulatory implications. In RCC, considerations as to whether all second primary malignancies or non-disease related deaths should be considered disease-free survival events are required to further specify study objectives and to determine the events needed for the final analysis.Table980PTableS-TRAC (N=615)PROTECT (N=1538)Clinical question of interestNumber of eventsHR (95% CI)Number of eventsHR (95% CI)Specific primary analysis – does the drug improve disease-free survival if no patient received therapy?2570.76 (0.59, 0.98)5130.80 (0.68, 0.95)Does the drug improve disease-free survival and delay the start of new therapy?2820.77 (0.61, 0.97)N/AN/ADoes the drug improve disease-free survival regardless of whether the patient had received new therapy?2890.81 (0.65, 1.02)5190.81 (0.68, 0.96)Does the drug improve recurrence free survival in no patient had received new therapy?2330.78 (0.60, 1.01)N/AN/A ConclusionsIn S-TRAC and PROTECT, there are similar treatment effects irrespective of the estimand selected and the clinical question asked. However, this may not be the case in all trials and considerations should be given to the clinical question of interest during trial design. Dialogue between all stakeholders is required and physicians will play a key role in such discussions to select the appropriate estimand. Clinical trial identificationNCT003756674 and NCT01235962. Editorial acknowledgementDavid Cope, PhD, of Engage Scientific Solutions and funded by Pfizer. Legal entity responsible for the studyPfizer. FundingPfizer. DisclosureD.J. George: Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Exelixis; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Merck; Research grant / Funding (self): Genentech/Roche; Research grant / Funding (self): Novartis; Research grant / Funding (self): Astellas; Research grant / Funding (self): Celldex; Research grant / Funding (self): Acerta; Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Innocrin Pharma; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb. M. Casey: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. E. Degtyarev: Full / Part-time employment: Novartis. M.J. Lechuga Frean: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. P. Aimone: Full / Part-time employment: Novartis. A. Ravaud: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Merck Sharp & Dohme. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): GlaxoSmithKline. All other authors have declared no conflicts of interest.

National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma

ObjectivesTo investigate outcomes of adjuvant therapy for serous and clear cell endometrial carcinoma, as prior studies are limited by sample size and/or patient heterogeneity. National guidelines permit substantial variations in treatment, suggesting the need for additional data. MethodsPatients with FIGO stages I–III serous or clear cell uterine carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant external beam radiation, brachytherapy, and chemotherapy were determined using SEER fields and Medicare claims. The primary outcome was death from endometrial cancer (cancer-specific mortality [CSM]) evaluated using Gray's test (univariable analysis, UVA) and Fine-Gray regression (multivariable analysis, MVA). ResultsA total of 1789 patients (1437 serous, 352 clear cell) were identified. In stages I–II patients (n = 1188), brachytherapy was significant for survival in UVA (P = 0.03) and MVA (P = 0.02). Additionally, in the subset with serous histology (n = 947), chemotherapy was also significant in UVA (P = 0.002) and approached significance in MVA (P = 0.05). The 4-year CSM for stages I–II serous cancers was 25% without brachytherapy or chemotherapy, 15% with one, and 9% with both (P ≤ 0.05 for all pairwise comparisons). In stage III patients (n = 601), chemotherapy was significant in UVA (P = 0.002) and MVA (P = 0.006). Most (81%) patients underwent lymph node dissection, which predicted lower CSM in stage III (P = 0.001) but not stages I–II patients. ConclusionsOur results suggest brachytherapy benefits stages I–II serous/clear cell cancers, chemotherapy benefits stage III serous/clear cell cancers, and both chemotherapy and brachytherapy benefit stages I–II serous cancers.

Patterns of Care and Outcomes of Adjuvant Treatment in Stage II Endometrioid Carcinoma

GOG 249 reaffirmed adjuvant pelvic radiation as the standard of care for high-risk early stage endometrial cancer. Patients with Stage II disease, elderly patients, and patients with poor performance status were underrepresented in the trial population. We utilized the National Cancer Database to study the patterns of care in stage II patients stratified by adjuvant therapy (AT), age, and performance status. We included patients diagnosed in 2004-2014 with stage II (FIGO 2009) endometrioid carcinoma who underwent TAH/BSO with negative margins. Patients with unknown AT, refusing AT, who died after surgery, or who did not have AT because of comorbidity were excluded. All patients with PXRT received a minimum dose of 45Gy and all patients with chemotherapy had multiagent chemotherapy (mCT). Adjuvant therapies compared were surgery alone, mCT alone, VBT alone, PXRT alone, VBT+mCT, PXRT+VBT, PXRT+VBT+mCT. Multivariate Cox regression was used to identify factors significantly associated with overall survival. A total of 5,130 patients were identified with tumor grades 42% G1, 29% G2, 18% G3, and 13% unknown. Lymphovascular invasion (LVI) was present in a small number of patients (14.5%, absent 34.1%, unknown 51.5%). Approximately one quarter of patients were >70 years old (1,232; 24%) and had 1+ comorbidity (1,341; 26%). More than one in four patients (1,492; 29%) did not receive any planned adjuvant therapy. These patients were older >65 (49% vs. 38%), Medicare insured (47% vs 39%), had 1+ comorbidity (31% vs.24%), and lived >50 miles from a treating facility (19% vs 12 %). For adjuvant therapy, 1,231 (24%) had VBT alone, 1,231 (23.5%) PXRT+VBT, 886 (13%) PXRT alone, 140 (3%) mCT alone, and 137 (3%) PXRT+VBT+mCT. The use of mCT+ VBT tripled from 1.8% prior to 2009 to 6.2% after 2009, while PXRT+VBT decreased from 28% to 20.5% in the same time period (all p < 0.001). For the entire cohort, median follow-up was 58.7 mos (95% CI: 57.1–60.1 mos) and 5-yr OS was 79.5% (78.2–80.9%). By adjuvant treatment 5-yr OS was 87.4% VBT+mCT, 84.3% VBT alone, 83.3%, PXRT+VBT, 79.9% PXRT+VBT+mCT, 79.6% mCT, 78.1% PXRT alone, 72.2% surgery alone. On adjusted multivariate survival models, mCT+VBT was not associated with improved OS over PXRT+VBT (adjusted HR 0.68, p=0.1). All adjuvant regimens had a significant survival advantage when compared to surgery alone except mCT alone. In subgroup of elderly patients >70 years and the subgroup of patients with 1+ comorbidity, 35% and 31% patients respectively had no planned adjuvant therapy. These patients had significantly inferior OS compared to patients with AT (elderly: aHR 1.8 (1.5-2.2), p < 0.001; 1+ comorbidity aHR 2.0 (1.6-2.6), p<0.001). Adjuvant treatment for stage II endometrioid carcinoma is not administered to more than one quarter of patients in this national hospital-based. Patients without adjuvant treatment are older and have comorbidities. There appears to be survival benefit to adjuvant treatment in these populations.

Adjuvant radiotherapy and chemotherapy improve survival in patients with pancreatic adenocarcinoma receiving surgery: adjuvant chemotherapy alone is insufficient in the era of intensity modulation radiation therapy.

In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT‐RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population‐based, head‐to‐head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT‐RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT‐RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314–0.504) and 0.307 (0.235–0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone.

Evaluation of the outcome of adjuvant treatment for gastric cancer in Brazil and Peru: A retrospective study in two cancer centers in Latin America.

160 Background: Gastric cancer (GC) is one of the most frequent malignancies in developing countries. In Peru, it is the fourth most incident cancer, and the sixth one in Brazil. Mortality is still high. The chance of relapse of patients with non-metastatic disease undergoing surgery is more than 50%. It is suspected that Latin American patients present worse evolution compared to those treated in Asia or in developed countries, therefore it is fundamental to study factors related to the prognosis and evolution of patients with GC in our continent. We aimed to evaluate the outcome of adjuvant treatment for GC in patients from two countries with different racial miscegenation and eating habits, and correlate this with clinicopathological features. Methods: We retrospectively analyzed 187 patients with GC who underwent curative surgery and received CRT at AC Camargo Cancer Center (ACCCC) in Brazil and Instituto Nacional de Enfermedades Neoplasicas (INEN) in Peru. CRT was defined as MacDonald protocol. Primary endpoint was overall survival (OS). Cox regression model was performed in order to calculate hazard ratio (HR) and 95% confidence intervals (95%CI). Results: Median follow up time was 51 and 20 months in Brazil and Peru, respectively. Median age of our cohort was 54 years-old. Male sex was predominant in both countries (Brazil: 54.7%; Peru: 56.9%). Diffuse subtype also was predominant (Brazil: 58.3%; Peru: 55.1%). Median OS was 103.9 and 45.2 months in Brazil and Peru respectively (p &lt; 0.001). In the multiple analysis, we found that pathological stage (I/II vs. III; HR = 4.1, 95%CI 1.4-11.7; p = 0.009) was independent prognostic factor adjusted by country of treatment, histological subtype, localization, age and gender. Conclusions: Survival differences exist between Brazil and Peru. We observed that patients from Peru had more advanced pathological stage after surgery. This difference suggests a possible prognostic factor in OS. Ethnic/genetic factors, eating habits and other clinicopathological or molecular factors may also explain different prognosis. Future studies are warranted to determine these prognostic factors in Latin American gastric cancer patients.

Impact of Surgical Complications Following Resection of Locally Advanced Rectal Adenocarcinoma on Adjuvant Chemotherapy Delivery and Survival Outcomes.

Surgical complications after resection for locally advanced rectal cancer may influence adjuvant treatment outcomes and survival. Few studies have examined this effect. This study aimed to examine the impact of surgical complications on adjuvant therapy delivery and survival in patients with locally advanced rectal cancer treated with long-course chemoradiation followed by surgery. This is a retrospective analysis of a prospectively collected multicenter colorectal cancer database. Data were collected from the Australian Comprehensive Cancer Outcomes and Research Database. All patients who completed neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer between January 2003 and December 2014 were selected. We examined the types and frequency of surgical complications and their impact on the delivery of adjuvant chemotherapy and survival. Data were available for 517 patients, of whom 147 (28%) had a surgical complication. Patients with a surgical complication were less likely to commence adjuvant chemotherapy (33% vs 66%; p = 0.0005) and more likely to have adjuvant treatment commencing more than 8 weeks from surgery (71.8% vs 21.2%; p = 0.004). Wound-related complications (p = 0.001), return to operating theater (p = 0.004), and readmission within 30 days (p = 0.02) had the most significant negative impact on the delivery of adjuvant chemotherapy. Surgical complications were significantly more likely in males (31.6% vs 20.8%, p = 0.003) and laparoscopic converted cases (47.8% vs 21.8%, p = 0.03). For the entire patient population, adjuvant chemotherapy compared with surveillance was not associated with an improved recurrence-free survival (HR, 1.06; p = 0.83) but was associated with an improved overall survival (HR, 0.53; p = 0.04). This study was limited by its retrospective design. Surgical complications in patients having surgery following neoadjuvant chemoradiotherapy for locally advanced rectal cancer were associated with significantly reduced uptake and delays to receiving adjuvant therapy. Surgical complications, however, were not associated with either significantly reduced recurrence-free or overall survival. Adjuvant chemotherapy delivery was associated with improved overall survival.

Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials

Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged >70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens. Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (<70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage. DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and ≥70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity Index ≤1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National Cancer Institute Combined Index ≤1 and >1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores. Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.

Primary tracheal adenoid cystic carcinoma: adjuvant treatment outcome.

Adenoid cystic carcinoma (ACC) is the second most common tracheal tumor, but its optimal treatment strategy is still controversial. To further elucidate the impact of treatment on disease-free survival (DFS) and overall survival (OS), we retrospectively investigated different treatment modalities and outcomes of 56 patients with primary ACC of the trachea treated at four hospitals in Sichuan Province of China from 1995 to 2012. 52 patients were included in the analysis. 4 patients with unresectable tumors were treated primarily with radiotherapy (RT) alone. 11 of 48 patients who received surgery as primary therapy obtained complete resection without adjuvant therapy. 24 of 37 patients who had incomplete resection (R1, R2) received postoperative RT while 13 patients were treated without postoperative RT. Postoperative chemotherapy (CT) was used in 12 patients with postoperative RT. No significant difference was shown in DFS (p = 0.683) and OS (p = 0.829) between patients with complete resection and those with incomplete resection. Postoperative RT for patients with incomplete resection was associated with improved DFS (92 vs. 62 months, p = 0.027) and OS (125 vs. 78 months, p = 0.004). Postoperative chemotherapy (CT) following RT did not have a significant impact on DFS (p = 0.390) or OS (p = 0.646) in patients with positive margin. These observations suggest that postoperative RT should probably be recommended for patients with incomplete resection. Postoperative CT following RT in patients with incomplete resection did not seem to produce an additional survival benefit.

Abstract P1-08-13: Predictive value of intrinsic luminal subtypes in premenopausal women with endocrine-responsive early breast cancer: Results from Austrian breast and colorectal cancer study group trial 5

Abstract Purpose: The aim of the present study was to assess the predictive value of intrinsic luminal subtypes in premenopausal hormone receptor-positive early breast cancer patients who received adjuvant endocrine treatment or chemotherapy. Patients and Methods: Intrinsic luminal breast cancer subtypes were centrally assessed by immunohistochemistry on whole tissue sections of breast cancer patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5 and received either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 &amp;lt;20%, Luminal B/HER2-negative subtype as Ki67≥20%. Luminal B/HER2-positive subtype displayed HER2 overexpression by IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathological factors. Results: 155 (36%), 217 (50%) and 59 (14%) of 431 tumors were classified as Luminal A, Luminal B/HER2-negative and Luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with Luminal B tumors had a significantly shorter RFS (adjusted hazard ratio [HR] for recurrence: 2.29, 95% confidence interval [CI] 1.44-3.64, P &amp;lt; 0.001) and OS (adjusted HR for death: 3.97, 95% CI 1.94-8.08, P &amp;lt; 0.001) as compared to patients with Luminal A disease. No interaction between intrinsic luminal subtypes and treatment was observed (test for interaction: P = 0.42 for RFS; P = 0.32 for OS). Combination endocrine treatment with goserelin/tamoxifen tended to be more effective than CMF chemotherapy in both luminal A and luminal B subtypes. Conclusion: Intrinsic luminal subtype is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor positive breast cancer but is not predictive for outcome of adjuvant treatment with either goserelin/tamoxifen or chemotherapy with CMF. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-13.