Addition Of Adjuvant Chemotherapy Research Articles

Current Applications and Future Directions of Circulating Tumor Cells in Colorectal Cancer Recurrence.

The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30-50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools have limitations in the precise and early detection of cancer recurrence. Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream. These can provide real-time information on disease status. CTCs might become novel markers for predicting CRC recurrence and, more importantly, for making decisions about additional adjuvant chemotherapy. In this review, the clinical application of CTCs as a therapeutic marker for stage II CRC is described. It then discusses the utility of CTCs for monitoring cancer recurrence in advanced rectal cancer patients who undergo neoadjuvant chemoradiotherapy. Finally, it discusses the roles of CTC subtypes and CTCs combined with clinicopathological factors in establishing a multimarker model for predicting CRC recurrence.

Adjuvant Chemotherapy With or Without Radiotherapy for Resected Pancreatic Cancer After Multiagent Neoadjuvant Chemotherapy.

Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting. This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup. Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors. After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.

Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2- Breast Cancer.

Adjuvant endocrine therapy (ET) represents the standard of care for almost all hormone receptor (HR)+/HER2- breast cancers, and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is therefore a significant need for the integration of biological biomarkers in the choice of adjuvant ET beyond currently used clinicopathological characteristics. Several gene expression assays have been developed to identify patients with HR+/HER2- breast cancer who will not derive benefit from the addition of adjuvant chemotherapy. By enhancing risk stratification and predicting therapeutic response, genomic assays have also shown to be a promising tool for optimizing endocrine treatment decisions. In this study, we review evidence supporting the use of most common commercially available gene expression assays [Oncotype DX, MammaPrint, Breast Cancer Index (BCI), Prosigna, and EndoPredict] in tailoring adjuvant ET. Available data on the use of genomic tests to inform extended adjuvant treatment choice based on the risk of late relapse and on the estimated benefit of a prolonged ET are discussed. Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low-risk patients is reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

Role of adjuvant chemotherapy in patients with stage II-III ampullary cancer.

508 Background: Survival benefits for patients (pts) with ampullary cancer (AC) on adjuvant chemotherapy (ACT) remain unknown. Some studies support post-operative treatment, while others state the opposite. Also, there are no clear evidence indicating that histopathological types (pancreaticobiliary (PB-type) and intestinal (IN-type)) can be used to guide the adjuvant setting. The aim of this study is to assess the ACT efficacy in different histopathological types of ampullary adenocarcinoma (pathological stages II-III). Methods: 81 pts were enrolled in the study in total, 45.7% were males, median age was 66.0 (range 43.9-83.8) years. 36.9% were IN-type, 50.8% – PB-type, and 12.3% – mixed. Almost all (97.5%) pts underwent Whipple procedure. 50 pts (61.7%) received ACT: 78.0% – 5-FU-based regimen and 22.0% – gemcitabine-based. Results: There was no clinical benefit in pts administered with ACT in terms of overall survival (OS): median OS was 55.5 months versus 43.6 month in observation arm; p=0.93. The ACT (FU-based or gemcitabine-based) did not correlate to improve OS in patients with IN-type: 38.0 months in patients who received ACT versus 30.5 months in those who did not; p=0.75. The ACT has shown better survival benefit in patients with PB-type compared to observation, however there was no statistical difference: 21.1 and 43.6 months, respectively; p=0.52. 5-FU-based ACT did not show any benefits compared to gemcitabine-based therapy in this subgroup. Conclusions: The use of adjuvant chemotherapy (FU-based or gemcitabine-based) in patients with II-III stage ampullary cancer was not associated with improved overall survival in our trial. There was no clinical benefit from addition of ACT either despite the heterogeneity of the tumor tissue origin (IN-type or PB-type).

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study.

Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. The study enrolled a total of 1589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group [mean age, 64.0 (9.9) years; 766 (48.2%) were females and 823 (51.8%) were males]. All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 months, P =0.002) and CSS (33.0 vs. 27.0 months, P =0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P =0.003, HR=0.782; 95% CI, 0.667-0.917 for OS; P =0.004, HR=0.784; 95% CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.

Effect of Adjuvant Chemotherapy in Highly Malignant Non-Metastatic Prostate Cancer: An Interim Analysis of Non-Randomized Comparative Trials.

Gleason grade group 5 (GG5) prostate cancers is aggressive with high metastatic rates and is not sensitive to androgen deprivation therapy (ADT). Even the presence of a limited (tertiary) Gleason pattern 5 component may have high aggressive biological behavior. This study aims to prospectively evaluate whether a non-androgen receptor pathway therapy - adjuvant chemotherapy could improve clinical outcomes among non-metastatic prostate cancer with the above highly malignant characters. This prospective non-randomized clinical trial included non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or tertiary Gleason pattern 5. Each subject was allowed to decide whether to receive four to six cycles chemotherapy of docetaxel after receiving a standard treatment (i.e., radical surgery ± radiotherapy or radical radiotherapy combined with long-term ADT). The primary endpoint was event-free survival (EFS). Event was defined as any of biochemical failure or imaging failure, or change of systemic therapy due to PSA arises, or death. The secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. A total of 188 consecutive patients were enrolled from November 2019 to November 2022. Median prostate-specific antigen was 26.6 ng/ml. 52% had T3b to T4 disease, 27% had N1 disease. 140 patients received standard therapy only, and 48 patients received adjuvant chemotherapy after radical therapy. The median follow-up time was 18.4 (3.0-36.7) months. The estimated 36-month EFS of the chemotherapy group and the control group were 94.7% vs. 72.8% (p = 0.044). There were 1 event who added novel endocrine therapy in the chemotherapy group, and 21 events in the control group, including 6 cases of biochemical recurrence and 9 cases of lymph node and distant metastasis, 4 cases that changed systemic therapy and 2 cases died. The MFS of the two groups at 36 months were 100% and 90.7%, respectively (P = 0.143). After the 1:1 propensity score match, the EFS and MFS of the two groups were 94.7% and 80.8% (P = 0.069), and 100% and 93.1% (P = 0.132), respectively. The urinary toxicity of grade 2 and 3 in the chemotherapy group and the control group were 4.2% and 7.1% (P = 0.134) while the grade 2 rectal toxicity were 5.0% and 10.4% (P = 0.317), respectively. No grade 4 toxicity occurred. Considering the chemotherapy-related side effects, grade 3 or above toxicity were leukopenia (41.7%), alopecia (27.1%), thrombocytopenia (2.1%) and edema (2.1%). Results of this interim analysis shows that the addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall recurrence and metastasis free survival of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Prognostic relevance of tumor‑infiltrating lymphocytes in residual tumor tissue from patients with triple‑negative breast cancer following neoadjuvant chemotherapy: A systematic review and meta‑analysis.

Further adjuvant chemotherapy treatment can provide benefits to certain patients with triple-negative breast cancer (TNBC) that fail to achieve pathological complete response (pCR) after the administration of a neoadjuvant chemotherapy (NAC) regimen. However, biomarkers suitable for identifying patients likely to experience poor prognostic outcomes after undergoing additional adjuvant chemotherapy are currently lacking. Accordingly, the present meta-analysis was conducted to explore the relationship between tumor-infiltrating lymphocytes (TILs) or TIL subtypes (CD4+ or CD8+) in residual tumor (RT) tissue following NAC and TNBC patient prognosis. Relevant studies published through March 2023 were identified in Pubmed, The Cochrane Library, Embase and Web of Science databases. After excluding irrelevant studies, data were extracted from the remaining reports, while study quality was analyzed with the Newcastle-Ottawa Scale. Subsequent analyses were performed with Stata 14.0 and Review Manager 5.3. In total, seven relevant studies incorporating 1,202 patients were identified, all of which were retrospective cohort studies. Pooled analyses demonstrated that those patients exhibiting higher levels of RT TIL infiltration following NAC exhibited significantly improved recurrence-free, metastasis-free and event-free survival (RFS/MFS/EFS) compared with patients with lower RT TIL infiltration levels, together with an improved distant recurrence-free interval (DRFI) [hazard ratio (HR)=0.52; 95% confidence interval (CI)=0.39-0.69; P<0.00001]. In addition, patients exhibiting high RT TIL infiltration exhibited improved overall survival (OS) and breast cancer-specific survival (BCSS; HR=0.49; 95% CI=0.38-0.65; P<0.00001). Additional subgroup analyses revealed that patients with higher TIL infiltration levels or TIL subtype (CD4+ or CD8+) infiltration exhibited improved RFS/MFS/EFS/DRFI as compared with patients with lower levels of overall TIL or TIL subtype (CD4+ or CD8+) infiltration in RT tissue (HR=0.35, 95% CI=0.20-0.59, P<0.0001; HR=0.49, 95% CI=0.33-0.71, P=0.0002). Consistently, the OS/BCSS of patients exhibiting high levels of overall TIL or TIL subtype (CD4+ or CD8+) infiltration was increased compared with patients with lower levels of such infiltration (HR=0.33, 95% CI=0.19-0.59, P=0.0002; HR=0.55, 95% CI=0.41-0.76, P=0.0002). These data thus demonstrate that levels of overall TIL infiltration or infiltration by CD4+ or CD8+ TILs in RT following NAC can be used as a biomarker to reliably predict prognostic outcomes in patients with TNBC, in addition to highlighting possible targets that may guide the further immunotherapeutic management of these patients.

Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial

BackgroundFor locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC.MethodsThis is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2–4 weeks in the TNT group and 6–10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate.DiscussionThe TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients.Trial registrationCris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.

Epidemiology, survival, and treatment of liposarcoma subtypes: An analysis of the national cancer database.

e23535 Background: Liposarcomas are a soft tissue sarcoma which grow in adipose tissue, mainly in the subcutaneous fat of the limbs, and are the most common type of soft tissue sarcoma. Relatively little is known about the epidemiology, prevalence, and survival of various histological subtypes of liposarcoma, therefore, in the largest study to date, we analyzed this patient population using the NCDB. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Liposarcoma from 2004 to 2019 using the histology codes 8850, 8851, 8852, 8853, 8855, and 8858 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: We identified 19,351 patients with liposarcoma. Mean age at diagnosis was 59 years for all subtypes and 83.3% of patients were white. Well-differentiated tumors were the most common histological subtype (34.8%), conferred the longest overall survival, and were the largest tumors on average. Round-cell tumors were the rarest (2.4%) and had smaller average tumor size than other subtypes. Patients with the de-differentiated subtype (20.5%) experienced the lowest median survival (70.5 months; p &lt; 0.05) and an increased hazard ratio (HR = 2.8; p &lt; 0.05) after controlling for other subtypes, age, and stage at diagnosis. Surgery was the mainstay of therapy with 90% of patients receiving surgery. 11.2% received additional adjuvant chemotherapy and 2.8% received adjuvant radiotherapy. Round cell and Myxoid tumors were most amenable to resection (89.8% and 88.9% of patients having no residual tumor) compared to only 64.4% of dedifferentiated tumors with complete surgical resection. Conclusions: Liposarcomas are a heterogeneous group of tumors which carry unique patterns of presentation, treatment, and prognosis. Well differentiated tumors are common and amenable to treatment; de-differentiated tumors are more aggressive and remain difficult to fully treat.

The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment.

To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1mm) after neoadjuvant therapy (NAT). The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1mm margin clearance after NAT remains controversial. Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1mm and R 1 ≤1mm resections. Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005). The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1mm should be a primary goal in the surgical treatment of PDAC after NAT.

The use of neoadjuvant systemic therapies in breast cancer in Australia and New Zealand: Breast Surgeons of Australia and New Zealand quality audit.

Breast surgeons must maintain contemporary knowledge regarding appropriate referral for neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. To date, the greatest benefit is seen in stage II-III HER2-enriched and triple negative breast cancers (TNBC). This study is the first audit of use of NACT in Australia and New Zealand to stratify data by BC biological subtype. Prospective data from 116,745 patients between 2010 and 2019 was provided by the Breast Surgeons of Australia and New Zealand (BreastSurgANZ) Quality Audit (BQA) of Breast Cancer Care. Annual rates of NACT use were determined and change across time analysed with fractional regression. Data from 2018 to 2019 were combined and stratified by biological subtype (LumA, LumB HER2-neg, LumB HER2-pos, HER2 enriched, TNBC, Other basal-like), and age (<50, 51-74, and ≥75 years) and compared using negative binomial regression. The use of NACT increased annually (OR 1.26, P< 0.001), and the use of additional adjuvant chemotherapy (ACT) decreased (OR 0.78, P< 0.001). A significantly greater use of NACT was noted in patients with TNBC and HER2+ BC, and in all patients aged <50 years compared with older ages (P< 0.001), regardless of biological subtype. Increased uptake of NACT and decreased use of additional ACT is in keeping with progressive change in practice in response to contemporary evidence. Expansion of BQA data fields related to use of NACT, and detailed audit of NACT rates in Stage II-III TNBC and HER2 enriched BC will allow accurate determination of quality of practice in ANZ.

Abstract P2-03-06: Real world treatment of node negative low and intermediate recurrence score breast cancer

Abstract Introduction: Patients younger than 50 years old with node negative hormone receptor (HR) positive her2 negative breast cancer and oncotype Dx recurrence scores (RS) under 16 do not benefit from adjuvant chemotherapy. Those with a RS between 16-25 may have a marginal benefit from the addition of adjuvant chemotherapy, however a similar benefit may be achieved with adjuvant ovarian function suppression (OFS). The aim of this study is to describe real world treatment patterns and outcomes of premenopausal node negative patients with low and intermediate RS, with an emphasis on adjuvant OFS, endocrine therapy (ET), and menopausal status during adjuvant treatment. Methods: We retrospectively reviewed the records of all node negative patients under 50 years old who were sent for oncotype testing between 2008 and 2018. One hundred and sixty-five patients with low or intermediate RS were included in our analysis. Continuous variables were described using medians and interquartile range (IQR). Categorical variables were described as frequencies and percentages. Differences between categorical variables were analyzed with the chi squared test and survival was analyzed using the Kaplan-Meier method. The cox proportional hazards model was used to test the effect of multiple factors on survival. Breast cancer specific survival (bcss) was defined as the time to first breast cancer recurrence (local recurrence, second breast cancer, distant recurrence) and distant disease-free survival (ddfs) was defined as the time to any distant recurrence. Results: The median age was 44 (41-47) and median RS was 17 (14-20). Median follow-up time was 82 (61-108) months. One hundred and three (62.4%) patients had low clinical risk as defined in TailorX and 136 (82.4%) had intermediate RS. Fourteen (8.5%) patients with nodal micrometastases were also included. Only 5 (3%) patients received adjuvant chemotherapy and 74 (44.8%) received adjuvant OFS. Of the 91 (55%) of patients who did not received OFS, 21 (23%) went into menopause or underwent subsequent oopherectomy while on adjuvant ET. One hundred and three (62.4%) patients received adjuvant tamoxifen alone, 16 (9.7%) received an aromatase inhibitor alone, and 40 (24.2%) underwent an endocrine switch with all but 1 beginning treatment with tamoxifen. There were no significant differences in clinical risk or RS risk group between patients that received and did not receive OFS. There were 22 (13.3%) bcss recurrences. Twelve (7.2%) patients had a local recurrence, 5 (3%) patients had second breast cancers, and 5 (3%) had a distant recurrence as their first recurrence. Overall, only 6 (3.6%) patients had a distant recurrence. Both OFS and ET type were not significantly associated with bcss or ddfs. On univariate analysis menopause during ET was significantly associated with improved bcss (HR= 0.2, 95% CI 0.05-0.85), however on multivariate analysis it was no longer significant. Conclusion: With only 6 (3.6%) distant recurrences over a median follow-up of over 6.5 years node negative premenopausal women with low or intermediate RS treated in our institution show an excellent prognosis regardless of treatment type. Our results support the evidence that most of these patients do not need chemotherapy and suggests that most patients do not require OFS as well. Additional data examining the relationship between gene expression profiles and OFS benefit are needed to help guide OFS treatment in premenopausal patients who do not require chemotherapy. Citation Format: Opher Globus, Keren Levanon, Einav Nili-Gal Yam. Real world treatment of node negative low and intermediate recurrence score 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 P2-03-06.

Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol

PurposeMedulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients.MethodsAdult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed.ResultsForty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn’t statistically significant.ConclusionCombined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

Trends in receipt of adjuvant chemotherapy and impact on survival in resected biliary tract cancers

Background: Resection remains the cornerstone of curative-intent treatment for biliary tract cancer (BTC), however, recent randomized data support a survival benefit with the addition of adjuvant chemotherapy (AC) in these patients. Herein, we aimed to characterize trends and disparities in the utilization of AC and subsequent outcomes in gallbladder cancer and cholangiocarcinoma (CCA).

Comprehensive Genomic Profiling (CGP)-Informed Personalized Molecular Residual Disease (MRD) Detection: An Exploratory Analysis from the PREDATOR Study of Metastatic Colorectal Cancer (mCRC) Patients Undergoing Surgical Resection.

A majority of patients with metastatic colorectal cancer (mCRC) experience recurrence post curative-intent surgery. The addition of adjuvant chemotherapy has shown to provide limited survival benefits when applied to all patients. Therefore, a biomarker to assess molecular residual disease (MRD) accurately and guide treatment selection is highly desirable for high-risk patients. This feasibility study evaluated the prognostic value of a tissue comprehensive genomic profiling (CGP)-informed, personalized circulating tumor DNA (ctDNA) assay (FoundationOne®Tracker) (Foundation Medicine, Inc., Cambridge, MA, USA) by correlating MRD status with clinical outcomes. ctDNA analysis was performed retrospectively on plasma samples from 69 patients with resected mCRC obtained at the MRD and the follow-up time point. Tissue CGP identified potentially actionable alterations in 54% (37/69) of patients. MRD-positivity was significantly associated with lower disease-free survival (DFS) (HR: 4.97, 95% CI: 2.67–9.24, p < 0.0001) and overall survival (OS) (HR: 27.05, 95% CI: 3.60–203.46, p < 0.0001). Similarly, ctDNA positive status at the follow-up time point correlated with a marked reduction in DFS (HR: 8.78, 95% CI: 3.59–21.49, p < 0.0001) and OS (HR: 20.06, 95% CI: 2.51–160.25, p < 0.0001). The overall sensitivity and specificity at the follow-up time point were 69% and 100%, respectively. Our results indicate that MRD detection using the tissue CGP-informed ctDNA assay is prognostic of survival outcomes in patients with resected mCRC. The concurrent MRD detection and identification of actionable alterations has the potential to guide perioperative clinical decision-making.

Treatment and survival outcomes in older women with primary breast cancer: A retrospective propensity score-matched analysis

PurposeChanges in biological features and functional status make management decisions in older women with primary breast cancer complicated. We aimed to provide an overview of the clinicopathological characteristics and survival outcomes of older breast cancer patients based on the current treatment strategies. MethodsFemale patients diagnosed with primary invasive breast cancer at Fudan University Shanghai Cancer Centre from 2008 to 2016 were included. Patients were divided into a younger group (<65 years) and older group (≥65 years). Propensity score matching was utilised to generate balanced cohorts. ResultsA total of 13,707 patients met the study criteria. Compared with younger patients, older patients had a higher Charlson Comorbidity Index (p < 0.001), less lymph node metastasis (p = 0.009), more advanced tumour stage (p = 0.038), and a larger proportion of estrogen receptor-positive (p < 0.001) and epidermal growth factor receptor 2-negative (p < 0.001) tumours. Older patients were likely to receive mastectomy and axillary lymph node dissection in addition to a lower proportion of adjuvant chemotherapy. Adjuvant chemotherapy (HR [hazard ratio] 0.69, p = 0.039) was independently correlated with better overall survival in the older patients. This survival benefit (HR 0.58, p = 0.041) was confirmed in matched cohorts. Among the older patients with larger tumours (HR 0.48, p = 0.038) and more lymph node involvement (HR 0.44, p = 0.040), adjuvant chemotherapy was associated with a significant survival benefit. ConclusionOlder breast cancer patients showed less aggressive biological characteristics, intensive surgical and moderate medical preferences. The addition of adjuvant chemotherapy should be considered for older patients, especially for patients with large tumours and more lymph node involvement.

A case of early onset adenocarcinoma associated with colorectal polyposis with an unknown germline mutation

BackgroundTypically, in cases of adenomatous polyposis, colorectal cancer develops in the third or fourth decade of life. We report the case of a female patient with colorectal polyposis who developed adenocarcinoma at 8 years of age.Case presentationAn 8-year-old girl was admitted with a 4-year history of occasional bloody stools. Colonoscopy revealed colon polyposis and histopathological assessment confirmed a well-differentiated adenocarcinoma in the adenomatous polyps, so laparoscopy-assisted proctocolectomy was performed in the lithotomy position by a simultaneous abdominal and anal approach. To completely resect the rectal mucosa, excision was commenced just distal to the dentate line. After the mucosal resection up to the peritoneal reflection level, an inverted muscular cuff was cut circumferentially, and the terminal ileum was pulled through the muscular cuff and anastomosed to the anal canal. Histopathology revealed multiple adenomatous polyps and scattered well-differentiated tubular adenocarcinomas (tub1) in the adenomatous polyps and the non-polypoid mucosal lesions. Because complete resection was achieved, additional adjuvant chemotherapy was not administered. Polymerase chain reaction (PCR)-direct sequencing of the entire coding region and the exon–intron junctions, and real-time PCR of DNA extracted from blood cells, revealed no mutations of either APC or MUTYH. No deletions, duplications, translocations or inversions of APC, MUTYH and GREM1 genes were found using multiplex ligation-dependent probe amplification (MLPA) and G-banding analysis. Multi-gene panels sequencing for polyposis syndromes or hereditary colorectal cancers, and trio-whole exome sequencing was conducted. However, no candidate pathogenic variants of genes were detected in de novo dominant or autosomal recessive model. Somatic mutation of APC was not detected in 4 polyps by loss of heterozygosity analysis at a single nucleotide polymorphism in intron 14. The patient has remained disease-free for 5 years. Currently, the patient is on loperamide and passes stool 5 times/day without any soiling.ConclusionsThe genetic analysis suggests that she may have a germline mutation at unscreened region of these genes or in unidentified FAP gene. The patient will be carefully followed up for residual rectal carcinoma and for the development of other cancers.

Oncological Outcome of Conversion Surgery After Preoperative Chemotherapy for Metastatic Pancreatic Cancer.

To investigate the outcome of conversion surgery in patients with metastatic pancreatic cancer (mPDAC) and to identify patients who may benefit from this approach. The role of conversion surgery in patients with mPDAC and exceptional response to chemotherapy remains unclear. Patients who underwent surgical exploration for mPDAC following chemotherapy between 2006 and 2019 were included. Data on demographics, oncologic treatment, pathology, and postoperative outcomes were analyzed. Univariate and multivariate survival analyses were performed. Some 173 patients received preoperative chemotherapy and underwent surgical exploration. Ninety-three patients underwent resection of the primary tumor and metastatic sites, 80 patients underwent exploration only. In the resection subgroup, 45 patients had complete pathological response of metastases (ypM0) and 48 patients had residual metastases (ypM1). ypM0 status was associated with lower carcinoembryonic antigen levels and lower ypN stage. Overall survival after resection was 25.5 months in ypM0, 10.7 months in ypM1, and 8.1 months in patients without resection ( P <0.001). Additional adjuvant chemotherapy was significantly associated with prolonged survival in resected patients (29.0 vs 14.8mo, P =0.024) as well as in ypM0 (29.1 vs 19.2mo, P =0.047). Multivariable analysis identified conversion surgery, carbohydrate antigen 19-9 (CA19-9) and time of resection as independent prognostic markers for the entire cohort. CA19-9, ypM0 and adjuvant treatment were independent predictors of survival in the resection subgroup. In patients with mPDAC and ypM0 status after chemotherapy, surgical resection is associated with encouraging survival. mPDAC patients with exceptional response to chemotherapy may be candidates for exploration and for resection in ypM0. Adjuvant chemotherapy may provide an additional survival advantage.

Staging locally advanced cervical cancer with FIGO 2018 versus FIGO 2008: Impact on overall survival and progression-free survival in the OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274).

5531 Background: The International Federation of Obstetrics and Gynecology staging system for cervical cancer (FIGO 2008) was revised in 2018 to incorporate lymph node involvement (FIGO 2018). OUTBACK is an international, randomized phase 3 trial of adjuvant chemotherapy versus observation after standard of care treatment with chemoradiation for women with locally advanced cervical cancer. OUTBACK found no benefit from the addition of adjuvant chemotherapy. We evaluated the effects of classifying participants with these 2 staging systems in the OUTBACK trial population. Methods: OUTBACK recruited April 2011 to June 2017 and staged participants according to FIGO 2008. Lymph node status, smoking status, age, race and histological subtype were documented at trial entry as important prognostic factors. We assessed the effects of stage grouping into stage I, II, and III/IVa with FIGO 2008 versus FIGO 2018, on progression-free survival (PFS) and overall survival (OS) at 5 years using Kaplan-Meier estimates, and in univariable proportional-hazards regression analyses, and in multivariable analyses adjusting for important prognostic factors and randomly allocated treatment. Results: All 919 study participants had complete data for staging according to the 2 staging systems and most prognostic factors for adjustment. Among all participants, the 5-year outcomes were PFS = 62% and OS = 72%. Classification according to FIGO 2018 rather than FIGO 2008 yielded higher 5-year PFS and OS in each stage group (see table for numbers of participants, PFS and OS for each stage group). Predictors of PFS in multivariable analysis included squamous vs non-squamous histology (HR 0.71 for FIGO 2008 and 0.74 for FIGO 2018), but not nodal involvement when FIGO 2018 was used. Both staging systems were the only independently significant prognostic factors in both univariable and multivariable analyses (all p &lt; 0.0001) for both PFS and OS. Conclusions: Compared to FIGO 2008, reclassifying pts by FIGO 2018 staging resulted in more pts being classified as stage 3 due to the incorporation of nodal status. Staging locally advanced cervical cancer using FIGO 2018 rather than FIGO 2008 resulted in higher PFS and OS in each stage grouping that reflected stage migration, not a true improvement in outcomes. FIGO stage remains the strongest predictor of overall survival after CRT but survival outcomes by stage in trials using the old vs new staging system are not comparable. Clinical trial information: ACTRN12610000732088. [Table: see text]

Utility of adjuvant chemotherapy in early-stage, estrogen receptor-positive breast cancer patients under 50 years with a 21-gene recurrence-score of 16-25: A retrospective analysis using the National Cancer Database.

e12501 Background: The TAILORx trial showed that addition of adjuvant chemotherapy (AC) to endocrine therapy (ET) had no advantage in estrogen receptor (ER)+, HER2-, node negative (N0) breast cancer (BC) patients with an intermediate (11-25) 21-gene recurrence-score (RS). However, a subgroup analysis revealed that in women ≤ 50 years, AC had a lower rate of distant recurrence if the RS was 16-25. Using a large national database, we studied the utilization of AC in the aforementioned subset. Methods: The 2004-2018 National Cancer Database BC cohort was used to include female patients of 18-50 years. Inclusion criteria were N0, M0 patients with any T stage, RS 16-25, ER+/PR± and HER2-. Patients who received neoadjuvant chemotherapy were excluded. Logistic regression was used to evaluate AC utility trends. Kaplan-Meier (KM) and multivariate (MV) propensity score (PS) weighted Cox model were used to compare survival between patients without and with AC use. Results: Of the 15,792 patients, 4808 (30.45%) received AC. Median RS was 18 and 21 in patients without and with AC. Factors associated with AC use were higher T stage, poor and moderately differentiated tumors, age &lt;40, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node (RLN) surgery, ET and Radiation Therapy (RT). KM survival at 10 years was better with AC [96.2% vs 91.6%]. Patients without AC had worse survival [Hazard Ratio (HR)=1.683, 95% Confidence Interval (CI): 1.392-2.036, p&lt;0.0001] (Table). Conclusions: In this analysis,AC use had a 5% improvement in 10 year overall survival, in contrast to TAILORx trial which only showed a disease free survival benefit. Whether the benefit was due to direct cytotoxicity or ovarian function suppression effect of AC remains to be seen. In clinical practice, AC use is determined based on patient and tumor characteristics. Limitations of our study include non-population-based data and the possibility of cofounding despite the use of PS matching. [Table: see text]