Administration Of Adjuvant Chemotherapy Research Articles

Impact of delay in adjuvant chemotherapy administration for patients with advanced-stage epithelial ovarian carcinoma undergoing primary debulking surgery with bowel resection

<h3>Objectives:</h3> Patients with epithelial ovarian carcinoma (EOC) undergoing primary debulking surgery (PDS) with small or large bowel resection have a higher risk of postoperative complications that could delay administration of adjuvant chemotherapy. The aim of the present study was to evaluate the impact of chemotherapy delay in the survival of patients with EOC undergoing bowel resection using a hospital-based database. <h3>Methods:</h3> The National Cancer Database (NCDB) was accessed and patients diagnosed between 2004-2015 with stage III-IV EOC without a history of another tumor who underwent PDS that included small or large bowel resection with known surgery-chemotherapy interval and at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received multi-agent chemotherapy 2-6 week (group 1), 7-9 weeks (group 2) and 10-12 weeks (group 3) from surgery with the log-rank test. A Cox multivariate model was constructed to control for confounders. Impact of chemotherapy delay was also evaluated among patients who achieved complete gross resection (CGR) and those who had macroscopic disease. <h3>Results:</h3> A total of 9274 patients who met the inclusion criteria were identified; 69.8% received adjuvant chemotherapy 2-6 weeks from surgery while 24.5% and 5.7% received chemotherapy 7-9 weeks and 10-12 weeks respectively. Patients in group 2 (30.2%) and 3 (36.6%) were more likely to experience a prolonged hospital stay (>10 days) following PDS compared to those in group 1 (19.4%), p<0.001. Rates of unplanned re-admission within 30-days from surgery in group 1,2 and 3 were 7.7%, 9.2% and 11.3% respectively, p=0.002. Median OS for patients in group 1 was 44.78 months compared to 42.25 and 39.89 for those in groups 2 and 3 respectively, p=0.103. After controlling for patient age, race, presence of comorbidities insurance, tumor histology and stage, compared to patients in group 1 those in group 2 (HR: 1.04, 95% CI: 0.98, 1.10) and group 3 (HR 1.05, 95% CI: 0.94, 1.17) did not have worse survival. Status of residual disease was available for 3659 patients; 46% achieved CGR. For patients with CGR, median OS for those in group 1 and 2 was 55.46 and 52.70 months compared to 42.18 for those in group 3, p=0.015. After controlling for aforementioned variables those in group 3 had worse survival (HR: 1.37, 95% CI: 1.04, 1.82) compared to patients in group 1 while there was no difference in survival between group 2 and 1 (HR: 1.06, 95% CI: 0.90, 1.27). For patients with macroscopic residual disease, timing of chemotherapy administration was not associated with survival; median OS for patients in group 1, 2 and 3 was 41.3, 42.74 and 41.13 months respectively, p=0.82. <h3>Conclusions:</h3> For patients with advanced stage EOC undergoing PDS with bowel resection extreme delay in adjuvant chemotherapy administration over 10 weeks from surgery may be associated with a negative impact on the survival of those who achieve CGR.

Role of adjuvant chemotherapy for patients with FIGO stage I high-intermediate risk endometrial carcinoma with lymph-vascular invasion

Objectives: Evaluate if the addition of adjuvant chemotherapy to radiation therapy improves survival of patients with high-intermediate stage I endometrioid endometrial carcinoma with lympho-vascular invasion (LVSI). Methods: Patients without a history of another tumor, diagnosed between 2010 and 2015 with pathological stage I endometrioid endometrial adenocarcinoma with LVSI who underwent hysterectomy with at least 10 lymph nodes removed, and met the GOG-99 criteria for high-intermediate risk were identified in the National Cancer Database. Those who received adjuvant radiation therapy with or without adjuvant chemotherapy (defined as treatment received within 6 months from surgery) and had at least one month of follow-up were selected for further analysis. Overall survival (OS) was compared with the log-rank test following generation of Kaplan-Meier curves. A Cox multivariate model was constructed to control for confounders. Results: A total of 2342 patients who met the inclusion criteria were identified; 1938 (82.7%) patients received radiation therapy only (RT) while 404 (17.3%) received chemoradiation (CRT). The majority (74.9%) of patients received brachytherapy (VBT) while 16.8% received external beam radiation therapy (EBRT), and 8.3% received combination of both VBT and EBRT. Rate of adjuvant chemotherapy administration did not differ based on the type of radiation therapy administered; 17.9%, 17% and 17.9% for patients who received EBRT, VBT or combination of both respectively, p=0.88. Patients who received CRT were younger (median age 62 vs 65 years, p<0.001) and more likely to have private insurance (58.2% vs 45.2%, p<0.001), stage IB (79.2% vs 71.3%, p=0.001) and grade 3 tumors (53.7% vs 24.6%, p<0.001). There was no difference between the two groups in terms of tumor size, patient race, presence of comorbidities, type of treatment facility, p>0.05. Median follow-up in the RT and CRT groups was 41.0 and 45.2 months respectively. There was no difference in OS between patients who received RT and CRT, p=0.53; 4-year OS rates were 85.8% and 82.6% respectively. CRT did not confer a survival benefit for grade 2 (p=0.98) or grade 3 (p=0.34) tumors. After controlling for patient age, race, insurance status, presence of comorbidities, tumor grade, size, and depth of myometrial invasion, CRT was not associated with better survival (HR: 0.95, 95% CI: 0.71, 1.28). Conclusions: In a large cohort of patients with high-intermediate risk FIGO stage I endometrioid endometrial adenocarcinoma with lymph-vascular invasion, the addition of chemotherapy to radiation therapy was not associated with a survival benefit. Evaluate if the addition of adjuvant chemotherapy to radiation therapy improves survival of patients with high-intermediate stage I endometrioid endometrial carcinoma with lympho-vascular invasion (LVSI). Patients without a history of another tumor, diagnosed between 2010 and 2015 with pathological stage I endometrioid endometrial adenocarcinoma with LVSI who underwent hysterectomy with at least 10 lymph nodes removed, and met the GOG-99 criteria for high-intermediate risk were identified in the National Cancer Database. Those who received adjuvant radiation therapy with or without adjuvant chemotherapy (defined as treatment received within 6 months from surgery) and had at least one month of follow-up were selected for further analysis. Overall survival (OS) was compared with the log-rank test following generation of Kaplan-Meier curves. A Cox multivariate model was constructed to control for confounders. A total of 2342 patients who met the inclusion criteria were identified; 1938 (82.7%) patients received radiation therapy only (RT) while 404 (17.3%) received chemoradiation (CRT). The majority (74.9%) of patients received brachytherapy (VBT) while 16.8% received external beam radiation therapy (EBRT), and 8.3% received combination of both VBT and EBRT. Rate of adjuvant chemotherapy administration did not differ based on the type of radiation therapy administered; 17.9%, 17% and 17.9% for patients who received EBRT, VBT or combination of both respectively, p=0.88. Patients who received CRT were younger (median age 62 vs 65 years, p<0.001) and more likely to have private insurance (58.2% vs 45.2%, p<0.001), stage IB (79.2% vs 71.3%, p=0.001) and grade 3 tumors (53.7% vs 24.6%, p<0.001). There was no difference between the two groups in terms of tumor size, patient race, presence of comorbidities, type of treatment facility, p>0.05. Median follow-up in the RT and CRT groups was 41.0 and 45.2 months respectively. There was no difference in OS between patients who received RT and CRT, p=0.53; 4-year OS rates were 85.8% and 82.6% respectively. CRT did not confer a survival benefit for grade 2 (p=0.98) or grade 3 (p=0.34) tumors. After controlling for patient age, race, insurance status, presence of comorbidities, tumor grade, size, and depth of myometrial invasion, CRT was not associated with better survival (HR: 0.95, 95% CI: 0.71, 1.28). In a large cohort of patients with high-intermediate risk FIGO stage I endometrioid endometrial adenocarcinoma with lymph-vascular invasion, the addition of chemotherapy to radiation therapy was not associated with a survival benefit.

SO-22 Importance order of risk factors for mortality in colon cancer stage II: A multivariate adaptive regression spline (MARS) analysis

52,980 deaths from colon cancer are expected in the US in 2021. Early stages tend to fare better, but recurrence and death are possible. The use of adjuvant chemotherapy in Stage II colon cancer is considered on an individual basis. To make the decision, clinicians evaluate the presence of high-risk factors. Their relative order of importance for mortality risk is unknown. The National Cancer Database was queried for patients with colon cancer stage II. It includes approximately 70% of cancer cases in the US. 70,074 patients were included in the final analysis. MARS, a machine learning technique, was used to construct a model to predict survival in patients with Stage II colon cancer and to determine variable importance. Data were partitioned into training, validation and testing groups at a 3:1:1 ratio. Outcome variable was death. Based on previous literature, we included the following variables as predictors to train the model: tumor grade, T staging, number of lymph nodes examined, carcinoembryonic antigen (CEA) level, perineural and lympho-vascular invasion. Microsatellite instability and bowel perforation data were not available. To determine the importance of each variable, we used a relative importance score (0-100%) generated in the statistical package. An area under receiving operating characteristic (ROC) curve in the training and testing dataset was generated to determine fit of the model. A generalized cross-validation score (GCV) was used to select optimal number of base functions. Statistical analysis was conducted in Salford Predictive Modeler v. 8.3. Relative importance scores of the variables were as follows: 1. Number of lymph nodes examined (100%), 2. CEA level (82.2%), 3. T4 staging (50.34%), 4. Tumor grade (31.31%). 5. Lympho-vascular invasion (25.44%). Perineural invasion did not contribute to the model. The MARS model generated an ROC curve for the training dataset 0.6185 and for the testing dataset 0.6179. GCV score was 0.19204 and suggested 7 basis functions. The model generated two knots for number of lymph nodes examined, at 14 and 27 lymph nodes. Patients with less than 14 lymph nodes examined were most likely to die. This relationship persisted but tended to plateau between 14 and 27 lymph nodes examined. For CEA level, one knot was defined at 38. The value of CEA elevation was linearly correlated with death until 38 ng/ml, after this number the maximum increase in the risk of death was almost reached. According to our MARS model, the three most important risk factors associated with mortality in patients with colon cancer stage II are: 1. Less than 14 lymph nodes examined, 2. Elevated CEA level, and 3. T4 staging (vs T3), in that order. CEA level could be considered to be incorporated in national guidelines as an important risk factor to guide the administration of adjuvant chemotherapy. A prospective validation of CEA level as a mortality marker in patients with stage II colon cancer is needed.

Neoadjuvant treatment is always justified for small PDAC, especially for clinical T1? - Debate from the position of Pros

Surgical resection offers the best chance for long-term survival, and upfront surgery is the most universally accepted approach for potentially resectable PDAC. But the result is dismal, the median survival of patients undergoing curative pancreatectomy alone is 18 to 20 months, with a 5-year survival rate of 10%. The administration of adjuvant chemotherapy and possibly chemoradiation leads to an improvement in OS relative to pancreatectomy alone. Adjuvant therapy following pancreatectomy therefore currently represents standard of care for patients with resectable PDAC. But, Administration of planned adjuvant chemotherapy may be limited by postoperative complications and early recurrence. Unfortunately, as few as 50% of patients who undergo pancreatectomy nationwide actually receive postoperative therapy. In an effort to overcome these barriers, early delivery of chemotherapy was evaluated as an alternative treatment sequence strategy. So the neoadjuvant therapies have been proposed. Two major hypothetical risks have been pointed out for neoadjuvant chemotherapy (NAC). One is a possible increase in perioperative morbidity and mortality. Second is the possibility that disease may progress and become unresectable during the course of NAC. A nationwide survey suggested that neoadjuvant treatment might not worsen perioperative outcomes or might increase the chance for curative surgery. NAC offers several theoretical advantages over upfront surgery, including early delivery of systemic therapy for almost all patients intended for treatment, high tolerance of multi-agent regimens by patients and a higher negative-margin resection rate, leading to improve OS. A review of select trials for patients with localized PDAC has suggested increased OS, supporting the benefits. Of course to date, there are no prospective data providing the superiority of neoadjuvant strategy over upfront surgery for resectable PDAC. So neoadjuvant treatment is not always justified for small PDAC, up to now. Nevertheless, neoadjuvant treatment can be a practical treatment strategy, particularly for patients at high biological or perioperative risk.

BILCAP-study: Should patients with resected biliary tract cancer really receive adjuvant chemotherapy with capecitabine?

Abstract Objective According to the 2019 published ASCO guidelines patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy based solely on the results of the BILCAP trial. Aim of this work is to analyze the quality of the BILCAP trial. Methods Design, conduct, statistics and reporting of the study were analyzed according to the Delphi list and the CONSORT checklist. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Results Several shortcomings could be identified in the study regarding design, conduct, statistics and reporting. The BILCAP study is a randomized, controlled, multicenter, phase 3 study which was done across 44 specialist hepatopancreatobiliary centres in the UK. Despite the inclusion of high specialized centres, the number of included patients each year for each center is extremely low. In particular, a total of 447 patients were included by 44 centers over a period of 11 years, meaning that less than 1 patient was included in this study every year by each center. However, the analysis was not adjusted for center which was one of the stratification factors. Follow up treatment for patients who had disease recurrence was not recorded. Randomization procedure is not well described. Minimization technique was adopted for stratification but mode of application is poorly reported and the choice of variables not justified. No blinding was present. Extensive power evaluations after adjusting the number of needed events, due to lower event rates than expected, were not done. For the observed HR = 0.81 with 234 events statistical power is only around 37%. 4 out of 9 items of the Delphi list and 6 out of 35 items of the CONSORT checklist were not properly addressed. According to the Cochrane Risk of Bias Tool (RoB 2) the overall risk-of-bias judgment for the outcome overall survival of the BILCAP study was “some concerns”. Almost all authors declared to have received funds from pharmaceutical companies, so a conflict of interest cannot be excluded. Additionally, the funding agency for this study (Cancer Research UK and Roche) had an advisory role in design and the first author of the BILCAP study was also involved in the generation of the ASCO guideline. Conclusion Based on the results of this study there is not enough evidence for the administration of adjuvant chemotherapy with capecitabine in patients with resected biliary tract cancer.

A novel 12-gene signature as independent prognostic model in stage IA and IB lung squamous cell carcinoma patients

There is currently no formal consensus on the administration of adjuvant chemotherapy to stage I lung squamous cell carcinoma (LUSC) patients despite the poor prognosis. The side effects of adjuvant chemotherapy need to be balanced against the risk of tumour recurrence. Prognostic markers are thus needed to identify those at higher risks and recommend individualised treatment regimens. Clinical and sequencing data of stage I patients were retrieved from the Lung Squamous Cell Carcinoma project of the Cancer Genome Atlas (TCGA) and three tissue microarray datasets. In a novel K-resample gene selection algorithm, gene-wise Cox proportional hazard regressions were repeated for 50 iterations with random resamples from the TCGA training dataset. The top 200 genes with the best predictive power for survival were chosen to undergo an L1-penalised Cox regression for further gene selection. A total of 602 samples of LUSC were included, of which 42.2% came from female patients, 45.3% were stage IA cancer. From an initial pool of 11,212 genes in the TCGA training dataset, a final set of 12 genes were selected to construct the multivariate Cox prognostic model. Among the 12 selected genes, 5 genes, STAU1, ADGRF1, ATF7IP2, MALL and KRT23, were adverse prognostic factors for patients, while seven genes, NDUFB1, CNPY2, ZNF394, PIN4, FZD8, NBPF26 and EPYC, were positive prognostic factors. An equation for risk score was thus constructed from the final multivariate Cox model. The model performance was tested in the sequestered TCGA testing dataset and validated in external tissue microarray datasets (GSE4573, GSE31210 and GSE50081), demonstrating its efficacy in stratifying patients into high- and low-risk groups with significant survival difference both in the whole set (including stage IA and IB) and in the stage IA only subgroup of each set. The prognostic power remains significant after adjusting for standard clinical factors. When benchmarked against other prominent gene-signature based prognostic models, the model outperformed the rest in the TCGA testing dataset and in predicting long-term risk at eight years in all three validation datasets. The 12-gene prognostic model may serve as a useful complementary clinical risk-stratification tool for stage I and especially stage IA lung squamous cell carcinoma patients to guide clinical decision making.

Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

BackgroundPrecise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.MethodsFrom September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.ResultsPreoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.ConclusionsPostoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.

Multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine: A case report

FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab is the preferred first-line treatment for right-sided metastatic colorectal cancer with RAS mutation. However, severe adverse events are common in Japanese patients. We report the successful management of multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine. A 68-year-old man presented with epigastralgia and appetite loss and was diagnosed with multiple stage IV colorectal cancers. Colonoscopy identified type II tumors in the ascending colon, sigmoid colon, and upper rectum. Histopathological examination of a biopsy specimen revealed well- to moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen showed multiple pulmonary nodules and para-aortic lymph node swelling. Laparoscopic loop-ileostomy was performed to avoid bowel obstruction due to severe stenosis of ascending colon cancer. Intraoperative observation revealed two white nodules suggestive of metastasis in the lateral area of the liver. Therefore, we diagnosed multiple stage IV colorectal cancers with multiple metastases (lung, liver, and distant lymph nodes). His postoperative course was uneventful, and chemotherapy was started. Since the cancer cells harbored a RAS mutation, he received FOLFOXIRI plus bevacizumab. Japanese Kampo medicine consisting of Hangeshashinto and Juzen-taiho-to, to prevent diarrhea and fatigue, was administered daily. After 12 courses of chemotherapy, though circumferential stenosis still existed in the ascending colon, the tumors in the sigmoid colon and upper rectum were unclear. Enhanced computed tomography showed shrinkage of the pulmonary nodules and para-aortic lymph node; therefore, laparoscopic-assisted ileocecal resection was performed. The postoperative histopathological examination revealed moderately differentiated adenocarcinoma. The patient recovered uneventfully, and Kampo medicine consisting of Ninjin'yoeito was administered for postoperative weakness. Administration of adjuvant chemotherapy in this patient led to a near complete response that has been maintained without recurrence for 2 years and 8 months without reduced quality of life.

Surgical Decision-Making in Pancreatic Ductal Adenocarcinoma: Modeling Prognosis Following Pancreatectomy in the Era of Induction and Neoadjuvant Chemotherapy.

To develop a predictive model of oncologic outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection after neoadjuvant or induction chemotherapy use. Early recurrence following surgical resection for PDAC is common. The use of neoadjuvant chemotherapy prior to resection may increase the likelihood of long-term systemic disease control. Accurately characterizing an individual's likely oncologic outcome in the perioperative setting remains challenging. Data from patients with PDAC who received chemotherapy prior to pancreatectomy at a single high-volume institution between 2007 and 2018 were captured in a prospectively collected database. Core clinicopathologic data were reviewed for accuracy and survival data were abstracted from the electronic medical record and national databases. Cox-proportional regressions were used to model outcomes and develop an interactive prognostic tool for clinical decision-making. A total of 581 patients were included with a median overall survival (OS) and recurrence-free survival (RFS) of 29.5 (26.5-32.5) and 16.6 (15.8-17.5) months, respectively. Multivariable analysis demonstrates OS and RFS were associated with type of chemotherapeutic used andthe number of chemotherapy cycles received preoperatively. Additional factors contributing to survival models included: tumor grade, histopathologic response to therapy, nodal status, and administration of adjuvant chemotherapy. The models were validated using an iterative bootstrap method and with randomized cohort splitting. The models were well calibrated with concordance indices of 0.68 and 0.65 for the final OS and RFS models, respectively. We developed an intuitive and dynamic decision-making tool that can be useful in estimating OS, RFS, and location-specific disease recurrence rates. This prognostic tool may add value to patient care in discussing the benefits associated with surgical resection for PDAC.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. The median follow-up was 7.2years, with a confidence interval (CI) of 7.1-7.3years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

Is Anti-Müllerian Hormone a Marker of Ovarian Reserve in Young Breast Cancer Patients Receiving a GnRH Analog during Chemotherapy?

Introduction: Anti-Müllerian hormone (AMH) is the most reliable biomarker of ovarian reserve; however, its role in predicting ovarian recovery after chemotherapy is unclear. Administration of a GnRH analog (GnRHa) during chemotherapy significantly reduces the ovarian failure rate and increases the pregnancy rate. The available data on the behavior of AMH during concurrent administration of chemotherapy and GnRHa are inconsistent. We investigated whether concurrent administration of triptorelin and adjuvant chemotherapy might reduce the expected drop of AMH. Methods: Eligible patients were premenopausal women aged <40 years, with a diagnosis of early breast cancer, and candidates to 4–8 cycles of adjuvant chemotherapy. Triptorelin (3.75 mg i.m.) was started before chemotherapy and administered every 4 weeks thereafter. The principal endpoint was the proportion of patients with an AMH percent change ≤50% between 12 months after chemotherapy and basal levels. The secondary endpoint was the proportion of patients achieving postchemotherapy AMH levels above the threshold of 0.2 ng/mL. Results: Fifty patients were enrolled, 31 of whom had blood samples available at baseline and 1 year after the end of chemotherapy. AMH decreased to nearly undetectable levels after chemotherapy and recovered after 12 months, but they did not exceed 1 tenth of the pretreatment levels. As for the secondary endpoint, 15 of the 31 patients recovered AMH levels above the threshold. Conclusions: This study did not reach its principal endpoint; however, the rate of 48% of patients who recovered AMH above threshold levels favorably compared with those in studies without concurrent GnRHa, supporting a better recovery of AMH with triptorelin.

Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology

PurposeAdjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved...

Effectiveness of Adjuvant Therapy in Patients with Pancreatic Cancer Who Underwent Neoadjuvant Therapy.

Neoadjuvant therapy (NAT) is used to treat not only advanced pancreatic cancer but also resectable lesions. The present study investigated the effectiveness of postoperative adjuvant chemotherapy for patients with pancreatic cancer who underwent surgical resection after NAT. Patients who underwent macroscopically curative resection after NAT for pancreatic cancer were enrolled. Adjuvant chemotherapy was defined as at least 1 cycle of planned chemotherapy within 3 months after the date of surgery and included S-1, gemcitabine, or both. We retrospectively examined the effect of adjuvant chemotherapy on overall survival (OS) and recurrence-free survival (RFS) as a function of patients' clinicopathological factors. Ninety-seven patients were included in the study, of which 68 (70.1%) underwent adjuvant chemotherapy. Administration of adjuvant chemotherapy was significantly associated with prolonged OS and RFS in patients whose elevated levels of carbohydrate antigen 19-9 or duke pancreatic monoclonal antigen type-2 did not normalize after NAT. In patients with pathological lymph node metastasis, the administration of adjuvant chemotherapy was significantly associated with longer OS but did not improve PFS. Postoperative adjuvant chemotherapy was associated with prolonged postoperative survival in patients with pancreatic cancer who did not sufficiently respond to NAT as judged by tumor marker expression.

Abstract SS1-10: Impact of Medicaid expansion on racial disparities in time to adjuvant chemotherapy administration among breast cancer (BC) patients

Abstract BACKGROUND: Delays in adjuvant chemotherapy initiation have a detrimental effect in outcomes and are more frequently seen among racial/ethnic minorities, uninsured patients and those with low socioeconomic status. A provision in the Affordable Care Act called for expansion of Medicaid eligibility in order to cover more low-income Americans. In this study we evaluate the impact of Medicaid expansion on racial disparities in time to adjuvant chemotherapy administration in a large cohort of BC patients.METHODS: Women (aged 40-64) diagnosed with primary invasive BC (stage I-III) between 01/01/2007 and 12/31/2016 were identified in the National Cancer Database. All patients underwent surgery as initial treatment modality and received adjuvant chemotherapy within 6 months of surgery. Chemotherapy delay was defined as &amp;gt;60 days from surgery to the first dose of chemotherapy. The cohort was limited to those residing in states that underwent Medicaid expansion in 2014 (KY, NV, CO, OR, NM, WV, AR, RI, AZ, MD, MA, ND, OH, IA, IL, VT, HI, NY, DE). For comparison purposes, 2007-2013 was considered the pre-expansion period and 2014-2016 the post-expansion period. We calculated difference-in-difference (DID) estimates using multivariable linear regression models. Results are presented as adjusted differences (in % points) between race/ethnicity groups in the pre and post-expansion periods, and as adjusted DID with 95% CI. A negative DID estimate indicates that Medicaid expansion reduces the racial/ethnic disparity in chemotherapy administration delay. The parallel trend assumption was tested. Variables in the final model included age, comorbidities, BC subtype, insurance status, distance to treatment facility, region, education, household income, facility type and facility case volume. RESULTS: 105,385 patients were included (median age 53), of them 75,663 (71.8%) were diagnosed in the pre- and 29,722 (28.2%) in the post-expansion period. 77.5% of the patients were White, 11.7% Black and 4.9% Hispanic. The proportion of patients experiencing chemotherapy initiation delays was greater among Blacks and Hispanics in both study periods compared to Whites. The proportion of chemotherapy delays decreased for all races between the pre and the post-expansion period. We observed a statistically significant decrease in the chemotherapy initiation racial disparity. The adjusted DID was -2% (95%CI -3.8 to -0.3, P=0.02) between Whites and Blacks was and -3% (95%CI -5.5 to -0.5, P=0.02) between Whites and Hispanics. In a subgroup analysis among 10,777 Medicaid patients the parallel trend assumption was not valid, therefore we estimated the DID between Whites and Blacks using a propensity-score based weight sample, identifying a reduction in the racial disparity of even greater magnitude (DID -9.1% [-14.4 to -3.8, P&amp;lt;0.001]). CONCLUSIONS: We demonstrate that Medicaid expansion reduced racial disparities by decreasing the proportion of Blacks and Hispanics experiencing delays in adjuvant chemotherapy initiation and decreasing the gap that exists when compared to Whites. These important results highlight the positive impact of policies aimed at improving equity and increasing access to health care. Pre-ExpansionPost-ExpansionRaceNAdjusted Rate of Delayed Chemo &amp;gt; 60 daysAdjusted Difference Between White Race (% points)NAdjusted Rate of Delayed Chemo &amp;gt; 60 daysAdjusted Difference Between White Race, (%points)Adjusted DID (95% CI), Percentage PointsPWhite5930527.202232524.20RefRefBlack856036.18.9372031.16.9-2.0 (-3.8 to -0.3)0.02Hispanic343232.35.1170426.32.1-3.0 (-5.5 to -0.5)0.02 Citation Format: Mariana Chavez-MacGregor, Xiudong Lei, Hui Zhao, Tina Shih, Sharon H Giordano. Impact of Medicaid expansion on racial disparities in time to adjuvant chemotherapy administration among breast cancer (BC) patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-10.

Full robotic multivisceral resections: the Modena experience and literature review

The robotic platform is becoming a multidisciplinary tool, versatile, and suitable for multiple procedures. Combined multivisceral resections may represent an alternative to sequential procedures with a potential favorable impact on postoperative morbidity, and on the timing of administration of adjuvant chemotherapy. We herein present our initial experience with full robotic multivisceral resections, and a review of the literature available. Between January 2018 and April 2020, 11 patients underwent multivisceral full robotic abdominal surgery: 4 patients presented with two synchronous tumors, 4 with primary cancer associated with a benign condition and 3 cases involved deep infiltrating endometriosis. Surgical teams enrolled were: General Surgery, Urology and Gynecology. A systematic bibliographic research up to April 2020 was conducted in PubMed. 4 colorectal resections combined with partial or radical nephrectomy were performed, as well as 2 right colectomies in combination with right adrenalectomy and gastric banding removal, 2 radical prostatectomies with Nissen Fundoplication and abdominal wall hernia repair, and 3 resections of deep pelvic endometriosis with colorectal involvement. Mean total operative time was 367min. No intraoperative complication or conversion to open was registered. Overall postoperative complication rate was 18.2%. 26 papers were included in the review (10 case series and 16 case reports) with a total of 156 combined multivisceral robotic procedures recorded. Robotic combined multivisceral resections proved to be safe and feasible when performed in high volume centers by expert surgeons. The heterogeneity of reports does not allow for a standardization of the procedure. Further studies and accumulation of experience are needed.

Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis.

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3–T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3–T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32–0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58–1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3–T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

Real-world patterns of adjuvant chemotherapy treatment for patients with resected pancreatic adenocarcinoma.

The aim of the study was to analyze the real-world treatment patterns of adjuvant chemotherapy administration among patients with resected pancreatic adenocarcinoma. Cases with non-metastatic pancreatic adenocarcinoma, diagnosed 2007-2018, treated with upfront surgical resection, and recorded within Alberta Cancer registry were accessed. Multivariable logistic regression analysis was conducted to evaluate factors predicting use of adjuvant chemotherapy. Kaplan-Meier survival estimates and multivariable Cox regression analysis were used to compare overall survival among patients treated with adjuvant gemcitabine versus those treated with adjuvant gemcitabine + capecitabine. A total of 695 patients who have undergone upfront surgical treatment of pancreatic adenocarcinoma, including 445 patients (64%) who received adjuvant chemotherapy and 250 patients (36%) who did not receive adjuvant chemotherapy. The following factors were associated with lower probability to receive adjuvant chemotherapy: older age (OR 0.94; 95% CI 0.93-0.96), node negativity (OR 0.47; 95% CI 0.33-0.67), higher Charlson comorbidity index (OR 0.86; 95% CI 0.74-0.99), and living within the Northern zone of the province (OR for Calgary zone versus North zone: 2.24; 95% CI 1.29-3.90). Within patients who received adjuvant gemcitabine ± capecitabine, factors associated with worse overall survival included higher Charlson comorbidity index (HR 1.18; 95% CI 1.00-1.40), and node-positive disease (HR for node-negative versus node-positive disease: 0.51; 95% CI 0.33-0.78). Type of chemotherapy was not predictive of overall survival (HR for gemcitabine versus gemcitabine plus capecitabine: 1.40; 95% CI 0.98-2.00). P value for interaction between type of chemotherapy and nodal status was 0.038. In this real-world study, the added benefit of adjuvant gemcitabine + capecitabine (compared to adjuvant gemcitabine) seems to be limited to patients with node-positive disease.

Synchronous resection of colorectal cancer primary and liver metastases: an outcomes analysis

BackgroundConcurrent resection of the primary cancer and synchronous colorectal cancer liver metastases (CRCLM) was evaluated for differences in outcomes following stratification of both the liver and colorectal resection. MethodsConsecutive cases of synchronous resection of both the CRC primary and CRCLM were reviewed retrospectively at a single, high-volume institution over a 17-year period (2000–2017). Results273 patients underwent simultaneous resection of CRCLM. The distribution of the primary lesion was similar between the colon (52.4%) and rectum (47.6%), while 46.9% of patients had bilobar liver disease. Major liver/major colorectal resection (n = 24) were significantly more likely to experience colorectal specific morbidity (OR 3.98, 95% CI 1.56–10.15, p = 0.004), liver specific morbidity (OR 7.4, 95% CI 2.22–24.71, p = 0.001), total morbidity (OR 2.91, 95% CI 1.18–7.18, p = 0.020) and 90-day mortality (OR 5.50, 95% CI 1.27–23.81, p = 0.023). Failure to receive adjuvant chemotherapy secondary to postoperative morbidity was associated with significantly worsened survival (HR for death 5.91, 95% CI 1.59–22.01, p = 0.008). ConclusionsPostoperative morbidity precluding the administration of adjuvant chemotherapy is associated with an increase in mortality. Combining a major liver with major colorectal resection is associated with a significant increase in major morbidity and 90-day mortality, and should be avoided.

Longitudinal analysis of cell-free mutated KRAS and CA 19\u20139 predicts survival following curative resection of pancreatic cancer

BackgroundNovel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRASmut) and CA 19–9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters.MethodsBetween 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Highly sensitive discriminatory multi-target ddPCR assays were employed to screen plasma samples for cfKRASmut. cfKRASmut and CA 19–9 dynamics were correlated with recurrence-free survival (RFS) and overall survival (OS). Patients were followed-up until 01/2020.ResultsOut of 25 enrolled patients, 76% had undergone R0 resection and 48% of resected PDACs were pN0. 17/25 (68%) of patients underwent adjuvant chemotherapy. Median follow-up was 22.0 months, with 19 out of 25 (76%) patients relapsing during study period. Median RFS was 10.0 months, median OS was 22.0 months. Out of clinicopathologic variables, only postoperative CA 19–9 levels and administration of adjuvant chemotherapy correlated with survival endpoints. cfKRASmut. was detected in 12/25 (48%) of patients, and detection of high levels inversely correlated with survival endpoint. Integration of cfKRASmut and CA 19–9 levels outperformed either individual marker. cfKRASmut outperformed CA 19–9 as dynamic marker since increase during adjuvant chemotherapy and follow-up was highly predictive of early relapse and poor OS.ConclusionsIntegrated analysis of cfKRASmut and CA 19–9 levels is a promising approach for molecular monitoring of patients following resection of PDAC. Larger prospective studies are needed to further develop this approach and dissect each marker’s specific potential.

Benefit of Adjuvant Chemotherapy After Radical Cystectomy for Treatment of Urothelial Carcinoma of the Bladder in the Elderly -An International Multicenter Study.

Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer, but approximately half of all patients will ultimately succumb to disease progression despite apparent cure with extirpative surgery. Elderly patients are at especially high risk of advanced disease and may benefit from perioperative systemic therapy. To assess the real-world benefit of adjuvant chemotherapy (AC) in patients ≥75 years old. We retrospectively reviewed patients who underwent RC for non-metastatic urothelial carcinoma of the bladder (UCB) from 12 participating international medical institutions. Kaplan-Meier survival curves and Cox regression models were used to assess the association between age groups, administration of AC and oncological outcome parameters such as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). 4,335 patients were included in the analyses, of which 820 (18.9%) were ≥75 years old. These elderly patients had a higher rate of adverse pathologic features. In an univariable subgroup analysis in patients ≥75 years with lymph node metastasis, 5-year OS was significantly higher in patients who had received AC (41% vs. 30.9%, p = 0.02). In a multivariable Cox model that was adjusted for several established outcome predictors, there was a significant favorable association between the administration of AC in elderly patients and OS, but no RFS or CSS. In this large observational study, the administration of AC was associated with improved OS, but not RFS or CSS, in elderly patients treated with RC for UCB. This is of clinical importance, as elderly patients are more likely to have adverse pathologic features and experience worse survival outcomes. Treatment of UCB should include both a multidisciplinary approach and a geriatric evaluation to identify patients who are most likely to tolerate and benefit from AC.