Administration Of Adjuvant Chemotherapy Research Articles

Nerve Anatomy Around Lumbo-aortic Lymphadenectomy by Retroperitoneal Approach

To describe the anatomy of the nerves during a laparoscopic retroperitoneal para-aortic lymphadenectomy with prioritization of their preservation. Demonstration of a nerve-preserving para-aortic lymphadenectomy. A 65-year-old woman with no significant medical history underwent diagnostic laparoscopy for evaluation of a right ovarian mass. In the absence of peritoneal carcinomatosis, bilateral adnexectomy wasperformed with pathology revealing a high-grade tubo-ovarian serous carcinoma. In accordance with French Guidelines for management of ovarian cancer, operative staging including pelvic and para-aortic lymphadenectomy was recommended [1]. Final pathology following staging surgery was consistent with stage IA high-grade serous ovarian cancer prompting administration of adjuvant chemotherapy postoperatively. We performed a lumbo-aortic lymphadenectomy with preservation of the following nerves: the superior hypogastric plexus, the lumbar splanchnic nerves and the sympathetic trunk. Although there are conflicting data as to the benefit of staging lymphadenectomy in women with presumed early stage high-grade serous ovarian cancer, current French Guidelines recommend its performance. When doing so, effort should be made to avoid injury to adjacent normal structures, and in doing so, minimize potential morbidity. The neural structures preserved in this case are part of the sympathetic contingent and participate in the innervation of the abdomen and pelvic viscera. The sympathetic contingent is responsible for the vasomotricity but is also involved in the contraction of the internal genitalia during orgasm and in the inhibition of the peristaltic contractions of the rectum. As such, its preservation may avoid certain postoperative complaints. When possible to do so without compromising essential elements of a cancer surgery, preservation of nerves should be considered.

The Role of Thoracic Surgery in Small Cell Lung Cancer – A Large Longitudinal Analysis (2002-2015) Based on Real-World Data

BackgroundMost SCLC patients are diagnosed with extensive disease (ED) and the prognosis in this cohort remains poor. However, some patients are diagnosed with limited (LD) or very limited (VLD, T1-2, N0-1, M0) disease and previous data suggest that surgical resection might improve outcomes in these patients. Most of the existing evidence comes from small case series. For this reason, we investigated clinical features and surgical outcomes in a large cohort of resected SCLC patients. Patients and MethodsWe used a large pseudomized dataset (n = 32432) provided by the Munich Cancer Registry to analyze all documented SCLC patients (n = 5043) between 2002 and 2015. We correlated patients’ characteristics as well as surgery modalities with survival data and describe trends in the role of surgery in SCLC over the time. ResultsWe analyzed 5043 SCLC patients. A total of 161 (3.2%) received either oncological (lobectomy, bilobectomy and pneumonectomy) or limited resection (segmentectomy and wedge resection). We found a significant trend suggesting that resections in SCLC patients become less common in all stages of disease, accompanied by an increased proportion of oncological resections. This suggests a more accurate preoperative staging. In VLD resection was significantly associated with longer survival compared to nonsurgical management (log-rank P = .013). Survival was better with oncological resection compared to atypical resection. Administration of adjuvant chemotherapy was associated with better outcome in all resected patients (P = .01). ConclusionVLD SCLC patients benefit from oncological resection. We recommend invasive staging in these patients to ensure VLD. Furthermore, adjuvant chemotherapy should be offered to all resected patients.

The impact of epidermal growth factor receptor mutation status on adjuvant chemotherapy for patients with high-risk stage I lung adenocarcinoma

ObjectiveThe aim of this study was to evaluate the role and effect of adjuvant chemotherapy based on epidermal growth factor receptor mutation status in patients with stage I lung adenocarcinoma. MethodsBetween 2010 and 2016, of 1901 patients with pathologic stage I (8th edition) non–small cell lung cancer, we identified 475 with high-risk (pT1c/T2a or positive for lymphovascular invasion) stage I lung adenocarcinoma who underwent lobectomy. We estimated propensity scores to adjust for confounding variables, including age, sex, Brinkman index, pulmonary functions, comorbidities, surgical approach, invasive component tumor size, visceral pleural, lymphatic, and vascular invasion, adenocarcinoma subtype, epidermal growth factor receptor mutation status, postoperative complications, and institution associated with the administration of adjuvant chemotherapy. The primary end point was recurrence-free survival. ResultsOf 292 patients without/unknown epidermal growth factor receptor mutation, 105 (36.0%) received adjuvant chemotherapy and 187 (64.0%) did not. In 69 pairs of patients who were propensity score matched, the 5-year recurrence-free survival was significantly better in those who underwent adjuvant chemotherapy (88.4%) than in those who did not (63.6%; P = .001). Of 183 patients with epidermal growth factor receptor mutation, 78 (42.6%) received adjuvant chemotherapy and 105 (57.4%) did not. In 49 pairs of propensity score–matched patients, there was no significant difference in the 5-year recurrence-free survival between those who underwent adjuvant chemotherapy (74.3%) and those who did not (80.5%; P = .573). ConclusionsThe effect of adjuvant chemotherapy for high-risk stage I lung adenocarcinoma varied by epidermal growth factor receptor mutation status. Epidermal growth factor receptor mutation status may help to identify patients with high-risk stage I lung adenocarcinoma who may benefit from adjuvant chemotherapy.

Nonmetastatic ypt0 rectal cancer after neoadjuvant treatment and total mesorectal excision: Lessons from a retrospective multicentric cohort of 383 patients

BackgroundA better understanding of pathological features and oncological survival in ypT0 rectal cancer after neoadjuvant chemoradiotherapy is required to improve patient selection criteria for rectal-preserving approach by local excision. Our aim was to define risk of lymph node metastasis and oncological outcomes in ypT0 rectal cancer after chemoradiotherapy and total mesorectal excision. MethodsAll consecutive patients who underwent total mesorectal excision for a nonmetastatic rectal adenocarcinoma classified ypT0 after neoadjuvant chemoradiotherapy, with or without locoregional lymph node involvement (ypN+ or ypN-), in 14 French academic centers between 2002 and 2015 were included. Data were collected retrospectively. Overall and disease-free survival were explored. ResultsAmong the 383 ypT0 patients, 6% were ypN+ (23/283). Before chemoradiotherapy, 86% (327/380) were staged cT3-T4 and 41% (156/378) were staged cN+. The risk of ypN+ did not differ between cT3-T4 and cT1-T2 patients (P = .345) or between cN+ and cN- patients (P = .384). After a median follow-up of 61.1 months, we observed 95% confidence interval (92%–97%) of 5-year overall survival and 93% confidence interval (91%–96%) of 5-year disease-free survival. In Cox multivariate analysis, overall survival was altered by intra-abdominal septic complications (hazard ratio = 2.53, confidence interval [1.11–5.78], P = .028). Regarding disease-free survival, ypN+ status and administration of adjuvant chemotherapy were associated with a reduced disease-free survival (P = .001 for both). cT3/T4 staging and cN+ staging did not modify overall survival (P = .332 and P = .450) nor disease-free survival (P = .862 and P = .124). ConclusionThe risk of lymph node metastasis and the oncological survival do not depend on the initial cT or cN staging in cases of ypT0 complete rectal tumor regression.

Consider Routine Administration of Neoadjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma – A Single Center Experience

Introduction: Major postoperative complications (MPC) after pancreatoduodenectomy limit adjuvant chemotherapy (AC) administration, which may factor in increasing use of neoadjuvant chemotherapy (NC) for resectable pancreatic ductal adenocarcinoma (PDAC). Here we examined effects of NC on outcomes and MPC on AC administration. Methods: We performed a retrospective chart review of patients who underwent pancreatoduodenectomy for PDAC at our institution, 2015-2020. Demographic, clinicopathologic, and postoperative variables were analyzed. Results: We identified 146 patients, 68 (47%) received NC (Table). NC patients had smaller tumors [median 2.4cm vs. 2.8cm, p<0.002]; higher R0 resection rates (94% vs. 85%, p=0.048); lower vascular invasion rates (35% vs. 71%, p<0.001); lower LODDS [log of positive to negative lymph nodes; -1.2 (-1.5-(-0.9) vs. (-0.8 (-1.3-(-0.4), p<0.001]. NC was not associated with MPC or AC administration. With 21 months median follow-up, there was a trend towards improved recurrence free survival (RFS) (median 40 vs. 24 months, p=0.327) in NC patients. Of 78 (53%) patients who did not receive NC, 13 (17%) experienced MPC, and AC receipt was lower in this group (80% vs 39% p=0.006), with a trend toward lower RFS (median 25 vs 16 months p=0.456). On univariate regression analysis, MPC were associated with lower AC administration rates, both in patients that received and did not receive NC (OR 0.091, p=0.002; and OR 0.156, p=0.006, respectively). Conclusions: NC before pancreatoduodenectomy for PDAC was associated with favorable pathology and a trend toward improved RFS. As MPC limits AC administration, NC should be considered for all patients with resectable PDAC.

Prognostic Factors of Granulosa Cell Tumors: A Retrospective Study in a Tertiary Care Cancer Centre of Eastern India.

Bhagyalaxmi NayakBackground and Aims The main objective of this study was to analyze the clinicopathological profile and prognostic factors of granulosa cell tumor (GCT). Method All the cases of ovarian cancer which were seen at our institute between January 2000 and December 2017 were reviewed. Data were analyzed with failure-free survival (FFS) as the primary end point. Results GCTs consisted of 2.66% of all ovarian cancers at our institute. The median age was 43 years. Majority of the patients (62.5%) were unstaged. Six patients (25%) had a fertility-preserving procedure. Forty two percent of the patients received adjuvant chemotherapy. Thirty eight percent of the patients developed recurrence. Considering tumor-related prognostic factors, there was a statistically significant decrease in FFS with the presence of hemorrhage ( p = < 0.001), larger tumors ( p = 0.042), and juvenile variant ( p = 0.002). On the contrary, when treatment-related factors were considered, there was no statistically significant improvement in FFS with the performance of lymphadenectomy ( p = 0.218), omentectomy ( p = 0.453), fertility sparing surgery ( p = 0.152), or administration of adjuvant chemotherapy ( p = 0.45). Conclusion Inherent tumor-related biological factors tend to play a more important role compared with treatment-related factors in GCTs. Hence, the traditional practice of performance of extensive staging procedures and routine adjuvant chemotherapy should be reviewed. Fertility-preserving surgery appears safe to be offered in early stages when desired. Although it is common knowledge that GCTs tend to be hemorrhagic tumors, this factor has not been well recognized as a prognostic indicator till date. Our study sheds some light on this aspect. Since these tumors have a tendency toward late recurrences, a long follow-up is prudent.

Distal Cholangiocarcinoma – Should we Shift the Treatment Paradigm?

Introduction: Systemic chemotherapy (SYS) is recommended in the management of pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA). Postoperative complications after pancreatoduodenectomy may limit adjuvant chemotherapy (AC) administration, therefore neoadjuvant chemotherapy (NC) is utilized increasingly for PDAC, but not dCCA. Here we examined the impact of SYS timing and postoperative complications on the receipt of SYS in patients undergoing pancreatoduodenectomy for PDAC and dCCA.

Stratified Prognostic Value of Pathological Response to Preoperative Treatment in yp II/III Rectal Cancer.

AimAccumulated studies have verified that tumor regression is associated with the prognosis of rectal cancer. However, stratified analysis within a certain stage is still unknown. The purpose of our study was to assess the impact of pathologic response on the survival of stageII and III rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT).MethodsClinicopathologic characteristics and tumor regression scores (TRS) were assessed in 236 rectal cancer patients who treated with nCRT followed by surgery. Survival analysis was performed using Cox proportional hazards models.ResultsAmong these patients, the stage of 88 patients was ypII, and 91 patients were with the stage of ypIII. The median follow-up time was 59.8 months. TRS was not an independent prognostic factor in ypII patients while it was significantly associated with the prognosis of ypIII patients (5-year survival rate 67.2% vs. 42.5%, P < 0.001). Furthermore, ypIII patients with the response to nCRT had similar survival to that of ypII patients (5-year survival rate 67.2% vs. 70.5%, P = 0.56). For ypIII patients, multivariable analysis showed that well differentiation, negative surgical margin, and the administration of adjuvant chemotherapy were associated with better survival. The surgical margin and differentiation were prognostic factors for ypII patients.ConclusionsypIII rectal cancer patients with poor response to preoperative treatment are at high risk of worse oncological outcomes.

The role of multiple bowel resections in advanced ovarian cancer: survival and surgical outcomes—a narrative review

: Ovarian cancer (OC) is the fifth most common cancer-related cause of death in women and the most lethal gynecologic malignancies in developed countries. In more than two thirds of the cases it is diagnosed as an advanced stage disease. The treatment requires a surgical step, aiming to remove the macroscopically visible disease, either as a primary debulking surgery or interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT). In both cases radical, complex and invasive surgical procedures are needed in order to achieve complete resection of the tumor, frequently involving bowel surgery. Considering the spread of the disease in the abdominal cavity, involvement of multiple bowel segments is common. Multiple bowel resections (MBR) are often needed to a complete cytoreduction but are linked to a higher rate of bowel diversion and postoperative morbidity, including severe postoperative complications, as anastomotic leakage (AL), and even death. These complications not only affect short term morbidity but may even postpone the administration of adjuvant chemotherapy, thus significantly affecting the outcomes of the treatment. NACT may help reducing the aggressiveness of debulking surgery and therefore the rate of its complications. This strategy represents a valid therapeutic option, especially in fragile patients, reducing the surgical related morbidity and the risk of bowel resections, without affecting the overall survival.

Adjuvant chemotherapy for visceral pleural invasion in 3-4-cm non-small-cell lung cancer improves survival.

Visceral pleural invasion (VPI) guidelines, for tumours ≤4 cm are ambiguous. Non-small-cell lung cancers (NSCLCs) 3 to ≤4 cm are assigned the T2a designation. Similarly, any tumours with VPI, smaller than 3 cm, are upstaged and also assigned the same T2a designation. We hypothesized that adjuvant chemotherapy would significantly improve 5-year survival for NSCLC ≤4 cm with VPI. The National Cancer Database was queried from 2010 to 2016 for cases of NSCLC with clinical stage I disease, ≤4 cm, who subsequently underwent surgical resection. These stage I NSCLCs were stratified according to clinical tumour sizes (0 to ≤1, 1 to ≤2, 2 to ≤3 and 3 to ≤4 cm). This cohort was then divided into groups with and without VPI and further split based on the administration of adjuvant chemotherapy. Kaplan-Meier analysis was used to calculate 5-year overall survival (OS) for patients categorized by tumour size, VPI status, and receipt of adjuvant chemotherapy. Multivariable Cox regression adjusting for tumour size and VPI status was used to determine associations between use of adjuvant chemotherapy and OS. A total of 61 454 patients with NSCLC and clinical tumour sizes <4 cm were identified and grouped based on size along with VPI and adjuvant chemotherapy. The 5-year OS for combined tumour sizes without VPI was higher than for patients with VPI (66.2% vs 59.5%, P < 0.001). The OS for tumour size (0 to ≤1, 1 to ≤2, 2 to ≤3 and 3 to ≤4 cm) was lower for patients with VPI regardless of size (all P ≤ 0.010). When all tumour sizes were combined, patients with VPI who received adjuvant chemotherapy had an improved 5-year OS compared to patients without adjuvant chemotherapy (65.5% vs 58.8%, P < 0.001). When cohorts were created by tumour size, only VPI tumours 3 to ≤4 cm had a statistically significant increase in 5-year OS for patients receiving adjuvant chemotherapy (68.8% vs 49.9%, P < 0.001). On multivariable Cox regression for OS, adjuvant chemotherapy was associated with significantly longer 5-year OS in tumour size 3 to ≤4 (hazard ratio = 0.62, 95% confidence interval 0.46-0.83, P = 0.001). VPI remains a poor prognostic factor in clinically node-negative, T2a or less, NSCLC patients. Guidelines recommend considering chemotherapy for high-risk T2aN0, margin-negative patients-including those patients with VPI. Based on the analysis, adjuvant chemotherapy should be considered specifically for 3 to ≤4 cm with VPI due to an observed 5-year OS advantage.

Relationship between diverting stoma and adjuvant chemotherapy in patients with rectal cancer: a nationwide study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

Patients at risk of recurrence after curative surgery for rectal cancer usually receive adjuvant chemotherapy. Postoperative recovery after low anterior resection (LAR) for rectal cancer can be improved by placement of a diverting stoma to reduce anastomotic leakage. However, it remains unclear how a diverting stoma affects administration of adjuvant chemotherapy in these patients. We identified Japanese patients with rectal cancer who underwent LAR in 2014 and received adjuvant chemotherapy within 12months of surgery in the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Doses of five types of chemotherapy administered (tegafur/uracil, tegafur/gimeracil/oteracil potassium, capecitabine, 5-fluorouracil, and oxaliplatin) were assessed according to the presence or absence of diverting stoma and the timing of stoma closure. There was no significant difference in the cumulative doses of chemotherapy administered in the 12months after LAR between patients with and without diverting stoma, but more doses were administered in the early postoperative period (0-2months after LAR) in patients without diverting stoma. Also, more doses of chemotherapy, regardless of type, were administered in the late closure group (7-12months after LAR) than in the early closure (≤ 6months) and no closure groups. Presence of a diverting stoma did not influence the dose of adjuvant chemotherapy administered within 12months after LAR but could have delayed the start of adjuvant chemotherapy. Patients with late closure of a diverting stoma received more doses of adjuvant chemotherapy administered over 12months.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

High-Risk Features Are Prognostic in dMMR/MSI-H Stage II Colon Cancer.

BackgroundHigh-risk features, such as T4 disease, bowel obstruction, poorly/undifferentiated histology, lymphovascular, perineural invasion, and <12 lymph nodes sampled, indicate poor prognosis and define high-risk stage II disease in proficient mismatch repair stage II colon cancer (CC). The prognostic role of high-risk features in dMMR/MSI-H stage II CC is unknown. Similarly, the role of adjuvant therapy in high-risk stage II CC with dMMR/MSI-H (≥1 high-risk feature) has not been studied in prospective trials. The aim of this analysis of the National Cancer Database is to evaluate the prognostic value of high-risk features in stage II dMMR/MSI-H CC.MethodsUnivariate (UVA) and multivariate (MVA) Cox proportional hazards (Cox-PH) models were built to assess the association between clinical and demographic characteristics and overall survival. Kaplan–Meier survival curves were generated with log-rank tests to evaluate the association between adjuvant chemotherapy in high-risk and low-risk cohorts separately.ResultsA total of 2,293 stage II CC patients have dMMR/MSI-H; of those, 29.5% (n = 676) had high-risk features. The high-risk dMMR/MSI-H patients had worse overall survival [5-year survival and 95%CI, 73.2% (67.3–78.1%) vs. 80.3% (76.7–83.5%), p = 0.0001]. In patients with stage II dMMR/MSI-H CC, the high-risk features were associated with shorter overall survival (OS) along with male sex, positive carcinoembryonic antigen, Charlson–Deyo score >1, and older age. Adjuvant chemotherapy administration was associated with better OS, regardless of the high-risk features in dMMR/MSI-H (log-rank test, p = 0.001) or not (p = 0.0006). When stratified by age, the benefit of chemotherapy was evident only in patients age ≥65 with high-risk features.ConclusionHigh-risk features are prognostic in the setting of dMMR/MSI-H stage II CC. Adjuvant chemotherapy may improve survival specifically in patients ≥65 years and with high-risk features.

Effect of Adjuvant Chemotherapy After SBRT for Node Negative, Non-Metastatic Non-Small Cell Lung Cancer

Administration of adjuvant chemotherapy (ACT) after surgical resection of a tumor ≥4cm is standard of care based on studies demonstrating improved overall survival. No such standard exists for tumors ≥ 4cm treated with stereotactic body radiation therapy (SBRT), and thus, administration of ACT remains variable across institutions. Using the National Cancer Database (NCDB), we aim to analyze overall survival (OS) in patients who undergo SBRT followed by ACT for localized non-small cell lung cancer (NSCLC). Additionally, we seek to identify predictors for receipt of ACT.Patients with node negative, non-metastatic NSCLC treated with definitive SBRT between 2004-2017 were identified from the NCDB. Patients were grouped into tumor size < 4cm or ≥4cm, and by use of ACT within 30 days of SBRT. Demographics were described by treatment. Logistic regression was used to assess the association between tumor size and treatment, adjusting for age, gender, race and comorbidities. Overall survival was calculated from date of end of radiation to date of death or last follow up. Multivariable Cox proportional regression was used to investigate the association between tumor size, treatment type, and OS, adjusting for the factors above.Of the 17441 patients identified meeting the inclusion criteria, 195 received ACT after SBRT (1.1%). Forty-nine percent of these patients were male, and 91% were white. The median age of patients who received ACT was 69. Twenty-six percent of the patients who received ACT had tumors ≥ 4cm (n = 51). There was a significant difference in hazard of death; patients with tumors ≥ 4cm without ACT (n = 1310) had worse OS as compared to those with tumors < 4cm without ACT (n = 15936) (HR 1.45; 95% CI 1.34-1.56, P < 0.0001). This difference became non-significant when comparing ≥4cm with ACT versus < 4cm without ACT (HR 1.17; P = 0.40). On pairwise comparison, there was no difference in hazard of death when comparing tumors ≥ 4cm with ACT versus ≥4cm without ACT (HR 0.81; P = 0.26). On multivariate analysis, tumor size ≥ 4cm was a significant predictor for receipt of ACT (OR 5.08; 95% CI 3.64-7.07, P < 0.0001). Older patients (OR 0.93 per 10yr increase; 95% CI 0.92-0.95, P < 0.0001) and those with comorbidities (OR 0.73 any vs no comorbidities; 95% CI 0.54-0.97, P = 0.032) were less likely to receive ACT. Notably, there was no difference between sex and race, white versus non-white, in administration of ACT.Patients with tumors ≥4cm treated with SBRT without ACT have decreased OS as compared to those with tumors < 4cm who are similarly treated without ACT. This survival decrement disappears when comparing tumors ≥4cm with ACT to tumors < 4cm without ACT suggesting a benefit to ACT. While there was no difference in OS between patients with tumors ≥4cm with or without ACT, this could be due to the small number of patients with tumors ≥4cm who received ACT. These findings identify a need to further study the roll of systemic therapy after SBRT.

The Role of Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma Patients with Pathological Positive Lymph Nodes After Neoadjuvant Chemotherapy Followed by Esophagectomy: a Single Institute Retrospective Analysis.

The need for adjuvant therapy after radical resection for patients with stage II–III thoracic esophageal squamous cell carcinoma (TESCC) who have undergone neoadjuvant chemotherapy (NAC) has not been determined. Since recurrence can occur after radical resection and since the prognosis is still poor, it is necessary to consider additional treatment strategies, including adjuvant chemotherapy. We retrospectively investigated the significance of adjuvant therapy after NAC followed by radical resection for TESCC. Between 2008 and 2018, 115 patients with clinical stage II–III underwent radical subtotal esophagectomy after neoadjuvant therapy. Among them, 62 were analyzed, excluding patients with T4 tumors and patients who had undergone R plus resection or who were receiving preoperative chemoradiotherapy. We compared patients who received adjuvant chemotherapy with those who only received observation; we examined overall survival (OS) and recurrence rates. Twenty-nine patients (46.7%) had lymph node metastasis, 12 of whom received adjuvant chemotherapy (41.3%). The recurrence rates for patients with and without lymph node metastasis were 55.1 % and 15.1%, respectively (p = 0.0022). Among patients with lymph node metastasis, there was no significant difference in the recurrence rate (p = 0.9270) or OS (p = 0.5416) based on the administration of adjuvant chemotherapy. However, in 15 patients with two or more positive lymph nodes, adjuvant chemotherapy increased OS (p = 0.0404). Adjuvant chemotherapy was associated with improved OS in clinical stage II–III TESCC patients with two or more pathological positive lymph nodes after NAC followed by radical surgery.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13193-021-01419-0.

Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival

<h3>Objectives:</h3> Administration of adjuvant chemotherapy within 42 days from surgery is one of the quality measures for ovarian cancer per SGO. The aim of the present study was to evaluate the impact of chemotherapy delay on the survival of patients with FIGO stage I epithelial ovarian carcinoma (EOC). <h3>Methods:</h3> The National Cancer Database (NCDB) was accessed and patients diagnosed between 2004-2015 with pathological stage I EOC without a history of another tumor who received multi-agent chemotherapy with known surgery-chemotherapy interval and had at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received multi-agent chemotherapy 1-6 weeks and 6-12 weeks from staging surgery with the log-rank test following generation of Kaplan-Meier curves. A Cox multivariate model was constructed to control for confounders. <h3>Results:</h3> A total of 8549 patients who met the inclusion criteria and received adjuvant chemotherapy at a median 35 days from surgery were identified; 67.7% received adjuvant chemotherapy 1-6 weeks from staging surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to be older than 65 years (21.8% vs 18%, p<0.001), with comorbidities (18.4% vs 14.9%, p<0.001), be managed in non-academic facilities (57.1% vs 53.2%, p=0.001), have government-issued insurance (32.7% vs 25.6%, p<0.001), stage IA (44.7% vs 40.1%, p<0.001), low-grade tumors (49.2% vs 45.6%, p=0.004), have a prolonged hospital stay (>10 days) (6.2% vs 2.3%, p<0.001) and an unplanned re-admission within 30-days from surgery (4.3% vs 2.7%, p<0.001). They were also less likely to be White (85.3% vs 89%, p<0.001), and undergo lymphadenectomy (80.7% vs 87.2%, p<0.001). Patients who experienced a delay had worse OS compared to those who did not, p<0.001; 5-year OS rates were 85.7% and 89.7% respectively. For patients with high-grade serous tumors, those who experienced a delay had a 5-yr OS of 81.9% compared to 88.6% for those who did not, p<0.001. After controlling for patient age, race, presence of comorbidities, insurance status, tumor histology and grade, performance of lymphadenectomy and substage, chemotherapy delay was associated with a worse survival (HR: 1.27, 95% CI: 1.12, 1.44). <h3>Conclusions:</h3> For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better survival.

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.