Neoadjuvant therapy in gall bladder cancer improves resectability and survival: a prospective study.

Efficacy of neoadjuvant therapy in gallbladder cancer: a meta-analysis using reconstructed time-to-event data.

Neoadjuvant and Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A 2020 Systematic Review and Meta-analysis, and Future Perspectives on Systemic Therapy

Gallbladder cancer is uncommon but highly fatal. Surgery remains the only potentially curative treatment for localized or locoregionally advanced gallbladder cancer. The rate of use of neoadjuvant and adjuvant chemotherapy in resectable gallbladder cancer is unknown. To assess factors associated with the use of neoadjuvant and adjuvant chemotherapy in patients with resectable gallbladder cancer and survival outcomes. The National Cancer Database was used to identify 6391 adults who underwent definitive surgical resection for gallbladder cancers between January 1, 2004, and January 1, 2016. Data analysis was performed from January 15 to February 15, 2020. Patients with localized or locoregionally advanced gallbladder cancers (ie, categories cTx-cT4, cN0-2, and cM0) were categorized as receiving neoadjuvant chemotherapy, adjuvant chemotherapy, or surgery alone. Categorical variables were compared using the χ2 test, with 1:3 nearest-neighbor propensity score matching based on neoadjuvant chemotherapy. Survival outcomes between groups were compared using Kaplan-Meier and Cox proportional hazards regression analyses. The use and survival outcomes of adjuvant and neoadjuvant chemotherapy. Of 6391 patients who underwent definitive surgery for gallbladder cancer, 4559 were women (71.3%); median age was 68 (IQR, 59-77) years. A total of 3145 patients (49.2%) received adjuvant chemotherapy, 3145 patients (49.2%) underwent surgery without chemotherapy, and 101 patients (1.6%) received neoadjuvant chemotherapy. Neoadjuvant chemotherapy use was associated with treatment at an academic facility (61 patients [60%] vs 38 patients [38%] treated in a nonacademic facility; P < .001) and in those with private insurance (65 patients [65%] vs 11 patients [11%] with Medicaid insurance; P < .001). Surgery alone was frequently used in older patients (median age, 72 [IQR, 63-81] years vs 59 [IQR, 52-66] years in patients with neoadjuvant chemotherapy; P < .001), those with Medicare insurance (1925 patients [57%] vs 1438 patients [43%] with adjuvant chemotherapy; P < .001), and patients with a higher comorbidity index score (326 patients [62%] vs 197 patients [38%] with adjuvant chemotherapy; P < .001). Adjuvant or neoadjuvant chemotherapy was used more frequently than surgery in patients with node-positive cancer (1482 [67.2%] vs 53 [65.4%] vs 912 [49.7%]). On propensity score matching analysis, adjuvant chemotherapy was associated with longer survival than surgery alone (22 vs 18 months, hazard ratio [HR], 0.78; 95% CI, 0.63-0.96); survival with neoadjuvant chemotherapy was not statistically significant compared with surgery alone and adjuvant chemotherapy groups (27 months, HR, 0.78; 95% CI, 0.58-1.04). However, in patients with node-positive gallbladder cancer, neoadjuvant therapy was associated with longer median overall survival (30 months [95% CI, 24-36 months] vs 14 months [95% CI, 11-17] in patients with surgery alone; P = .002). In this cohort study, use of adjuvant and neoadjuvant chemotherapy was low in patients with surgically resected gallbladder cancers. Chemotherapy was used more frequently than surgery in lymph node-positive disease compared with lymph node-negative disease. Adjuvant chemotherapy was associated with a survival advantage in resectable gallbladder cancer, and neoadjuvant chemotherapy was associated with increased survival in node-positive gallbladder cancers. These findings suggest that adjuvant chemotherapy and neoadjuvant chemotherapy should be considered in treatment of gallbladder cancer.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Gallbladder cancer is the most common malignancy of the biliary tract. Neoadjuvant chemotherapy (NACT) has improved overall survival by enabling R0 resection. Currently, there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer. As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients, we examined American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to determine if there was higher morbidity among the neoadjuvant group within the 30-day post-operative period. We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity. To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery. A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity (bile leak, infection rate, rate of converting to open surgery, etc.) compared to the group who only had surgery. To calculate the odds ratio for the primary and secondary outcomes, a crude logistic regression was performed. Of the 452 patients, 52 patients received NACT prior to surgery. There were no statistically significant differences in the odds of morbidity between the two groups, including bile leak [odds ratio (OR), 0.69; 95% confidence interval (95%CI): 0.16-2.10; P = 0.55], superficial wound infection (OR, 0.58; 95%CI: 0.03-3.02; P = 0.61), and organ space wound infection (OR, 0.63; 95%CI: 0.18-1.63; P = 0.61). There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

Gallbladder cancer (GBC) and cholangiocarcinoma (CCA) are rare entities with relatively poor prognoses. We compared treatment outcomes of definitive resection with or without neoadjuvant therapy in GBC and CCA patients. All non-metastatic GBC and CCA patients at a single institution who underwent definitive resection from 1992-2016 were analyzed. We compared overall survival (OS), locoregional failure (LRF) and distant failure (DF) in patients who received neoadjuvant therapy (chemotherapy and/or radiation) versus those who did not receive neoadjuvant treatment. OS was analyzed using the Kaplan-Meier method and log rank tests. Cox proportional hazard models were used to analyze time to recurrence. Out of 128 patients, 90 had GBC and 38 had CCA, 25 patients (27%) among GBC and 8 patients (21%) with CCA were T3, T4 or node positive. Overall, 52 (40%) GBC and 25 (20%) CCA patients received neoadjuvant treatment, chemotherapy alone 60 patients (47%) or radiation with or without chemotherapy 17 patients (13%). Chemotherapy was single agent in 44 patients (34%) and multi-agent in 25 (20%). The median OS for GBC patients was 3.1 years with 2.6 years for no neoadjuvant group and 3.1 years for neoadjuvant group (P=0.6786). Median OS was 2.6 years for CCA patients, 3.6 years for no neoadjuvant therapy versus 2.0 years for neoadjuvant group (P=0.1613). There was a trend towards increased DF in patients with CCA and GBC receiving neoadjuvant therapy: HR 2.74, 95% CI, 0.73-10.3, P=0.14 and 0.92, 95% CI, 0.44-1.93, P=0.82 respectively. The hazard ratio for time to LRF in CCA patients receiving neoadjuvant treatment was 3.17, 95% CI, 0.62-16.31, P=0.16 whereas HR was 0.15, 95% CI, 0.10-1.76, P=0.23 for GBC patients. Among GBC patients, the pattern of first failure was locoregional in 8 (10%) having 3 LRF in neoadjuvant group (2 with chemotherapy, 1 with CRT, 0 with RT alone) as compared to 5 in adjuvant group. Among 28 (35%) patients with DF first, 15 patients received neoadjuvant therapy versus 13 patients in non-neoadjuvant group. In CCA patients, LRF occurred first in 6 patients receiving neoadjuvant treatment (3 with chemotherapy, 1 with CRT, 2 with RT alone) as compared to 2 patients who were treated with non-neoadjuvant CRT. DF was the first site of failure in 9 patients treated with neoadjuvant CRT (8 with chemotherapy, 0 with CRT and 1 with RT alone) as compared to 4 patients without neoadjuvant treatment. In this retrospective data set, a trend towards better survival was seen in adjuvantly treated CCA patients, but not in GBC patients. Recurrence patterns also appear different among the two, which might be attributed to treatment modality used, patient selection or unmeasured factors. Gallbladder cancer (GBC); cholangiocarcinoma (CCA); neoadjuvant; resection; chemoradiation; chemotherapy.

Concurrent Chemoradiation Therapy for Resected Gall Bladder Cancers and Cholangiocarcinomas

Impact of Neoadjuvant Chemotherapy on the Postoperative Outcomes of Patients Undergoing Liver Resection for Colorectal Liver Metastases: A Population-Based Propensity-Matched Analysis

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer – A systematic review

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer - A systematic review

Introduction In patients with oesophageal cancer, little attention has been paid to the relevance of tumour invasion in blood (AI) and lymphatic vessels (LVI) as well as perineural invasion (PNI) after neoadjuvant therapy. Therefore, the aim of the present study was to assess the incidence and prognostic significance of these factors in a consecutive series of patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) who underwent neoadjuvant therapy followed by oesophagectomy. Method From a prospectively collected database, a consecutive series of patients was analysed. All patients with potentially curable adeno- or squamous cell carcinoma of the oesophagus or GOJ were treated with neoadjuvant chemotherapy or chemoradiation therapy followed by transthoracic oesophagectomy and two-field lymphadenectomy. The presence of AI, LVI and PNI was prospectively collected. Results Between January 2000 and September 2013, a consecutive series of 396 patients underwent a potentially curative oesophagectomy after neoadjuvant therapy for adeno- or squamous cell carcinoma. AI was seen in 150 (38%) of patients, LVI was seen in 203 (51%) of patients and PNI was seen in 204 (52%) of patients. 123 (31%) had no AI, LVI or PNI whatsoever. 96 (24%) had a combination of two out of three factors and 94 (24%) had presence of AI, LVI and PNI. The presence of AI, LVI and PNI was significantly (P = 0.001) related with ypT- and ypN-stage. Median overall survival was 170.8 months (95% CI: 68.9–272.8) if AI, LVI and PNI were all absent, 44.0 months (95% CI: 20.9–67.2) when one factor was present, 27.1 months (95% CI: 22.8–31.4) when two factors were present and 16.0 months (95% CI: 9.4–22.6) when AI, LVI and PNI were all present. On multivariate analyses the presence of AI, LVI and PNI or a combination of these factors were independent predictors. Conclusion These findings suggest the importance of the presence of AI, LVI and PNI after neoadjuvant therapy followed by oesophagectomy. The presence of AI, LVI and PNI should be incorporated in the standardised pathology report. It provides additional information for identyfying patients at high risk who may be candidates for adjuvant therapies. Disclosure of interest None Declared.

The Efficacy of Neoadjuvant versus Adjuvant Therapy for Resectable Esophageal Cancer Patients: Direct and Indirect Comparisons &lt;i&gt;via&lt;/i&gt; Meta-Analysis

4623 Background: The role of neoadjuvant chemotherapy (NAC) for resectable pancreatic cancer (RPC) remains controversial. We sought to compare the outcomes of NAC with upfront surgery (UFS). Methods: The study retrospectively enrolled patients with RPC who had UFS or received neoadjuvant FOLFIRINOX (FFX) or gemcitabine plus albumin-bound paclitaxel (GA). Between-group differences were assessed with T-test for continuous variables, and Chi-square / Fisher’s exact test for categorical variables. The overall survival (OS) and recurrence-free survival (RFS) were determined by the Kaplan-Meier method with Wilcoxon test for the difference between groups. The effects of NAC vs. UFS on OS and RFS were further estimated using Cox regression controlling the effects of age and CA 19-9. Results: Between 2011 and 2019, 131 patients with RPC underwent UFS followed by adjuvant chemotherapy (gemcitabine, n = 65; gemcitabine/capecitabine, n = 18; FFX, n = 9). Up to 32 patients (24.4%) could not receive adjuvant chemotherapy due to surgical complications or poor recovery. Total 50 patients with RPC received NAC (FFX, n = 32; GA, n = 18). Median of 5.5 cycles of FFX or 3 cycles of GA were given prior to surgery. Resection rate was 72% (FFX 62.5%; GA 88.9%). The rest (28%) were no longer surgical candidates due to disease progression rather than toxicities from NAC. On surgical pathological review, complete resection (R0) was achieved in 83.3% of resected cases after NAC (FFX 90%; GA 75%) and 79.4% with UFS. The tumor size distribution was: pT1 11.1%, pT2 41.7%, pT3 44.4% with NAC; pT1 5.4%, pT2 18.3%, pT3 76.3% with UFS. The nodal status distribution was: pN0 27.8%, pN1 55.5%, pN2 16.7% with NAC; pN0 23.7%, pN1 71.0%, pN2 5.3% with UFS. Median pre-treatment CA 19-9 was 321.95 unit/mL in the NAC group and 79.99 unit/mL in the UFS group (p = 0.009). Median age was 70.5 in the NAC group and 72 in the UFS group (p = 0.374). There was no significant difference in the performance status between the two groups. In Kaplan-Meier analysis, there was a significant difference of OS between UFS and NAC with median OS of 648 days under UFS versus 884 days under NAC (p = 0.029); the median of RFS was 390 days under UFS versus 392 days under NAC (p = 0.953). The hazard ratio (NAC vs UFS) adjusted for CA19-9 and age was 0.7 (p = 0.176) for OS and 0.98 (p = 0.918) for RFS. Conclusions: We observed a signal of tumor downstaging, higher R0 rate, and improved OS with NAC compared with UFS. Further prospective trials are needed to validate these results.

405 Background: Gallbladder cancer is a highly fatal disease with a high rate of recurrence even when diagnosed at an early stage. Because of its relative rarity, there are currently no established algorithms to guide therapy after cholecystectomy. To explore the value of adjuvant therapy with chemotherapy and radiation, we evaluated patients with resected gallbladder cancer treated at our institution. Methods: Patients diagnosed with gallbladder cancer who underwent cholecystectomy (simple or radical) between 2000 and 2010 were identified using our cancer registry. Retrospective chart review was performed for clinicopathologic data, including age, stage, grade, type of surgery, margin status, and type and duration of adjuvant therapy. The primary endpoint was overall survival (OS). Univariate (UVA) and multivariate (MVA) analysis was performed with Cox logistic regression analyses. Results: We identified 73 patients with a median followup for all patients of 28.2 months. The majority of patients were female (74%) and underwent radical cholecystectomy (64%). Positive margins and adjuvant radiation therapy were documented in 21% and 37%, respectively. The majority of patients did not receive any adjuvant therapy (53.4%). Median OS for all patients was 41.3 months. There was a survival benefit associated with patients undergoing radical cholecystectomy followed by adjuvant radiation (median OS 48.4 months vs. 22.3 months; HR 0.35; 95% CI: 0.13–0.98; p=0.0448) compared to simple cholecystectomy alone. On UVA, increasing age and positive margins were significantly associated with worse OS, while radical cholecystectomy was associated with improved OS. On MVA, increasing age, male gender, poorly differentiated tumor, and positive margins were associated with worse OS, while adjuvant radiation was associated with improved OS (p=0.0113). Conclusions: Our analysis supports the role for adjuvant radiation therapy in resected gallbladder cancer. Multi-institutional prospective studies should be performed to evaluate the optimal treatment strategy. Biomarker analysis might also help determine the subset of patients who would benefit from combined chemoradiation.

Comsplete resection is the primary treatment for retroperitoneal sarcomas (RPS). The role of neoadjuvant chemotherapy (NACT) in improving oncologic outcomes is currently under investigation in the STRASS 2 trial. This study assessed the association between change in tumor size or pathologic response and oncologic outcomes. Data were retrieved from the international Retroperitoneal Sarcoma Registry and included patients who had RPS treated with NACT between January 2017 and October 2020. The correlation between radiologic response (RECIST1.1), change in tumor size, pathologic response, and oncologic outcomes was evaluated. Binary logistic, Cox, and polynomial spline regression and log-rank tests were performed as statistical analyses. The study enrolled 141 patients from 14 medical centers. The most common histologies were dedifferentiated liposarcoma (36.9 %) and leiomyosarcoma (34 %). At completion of NACT, 14.5 % of the patients, had a partial response (PR), 63.3 % had stable disease (SD), and 22.2 % had progressive disease (PD). The hazard ratio of PD after NACT for overall survival (OS) was 1.9 (95 % confidence interval [CI], 0.9-4.1). A linear trend was observed between tumor growth and death rate. At early radiologic evaluation during NACT, PD was significantly associated, with worse OS (HR, 5.4; 95 % CI, 1.1-25.3). Partial response was significantly correlated with ≥20 % fibrosis/hyalinization (odds ratio [OR], 5.6; 95 % CI, 1.1-29.0). Progression in RPS on an early evaluation scan is associated with worse OS, and radiologic response is correlated with pathologic response based on fibrosis/hyalinization. A larger cohort is necessary for more significant associations between radiologic or pathologic response and oncologic outcomes.