Systemic Chemotherapy In Patients Research Articles

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial.

433 Background: In the ABC-trials, the 3-year overall survival (OS) was only 2.8% for patients with advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver who received systemic gemcitabine with cisplatin. Hepatic arterial infusion pump (HAIP) combined with systemic chemotherapy had a pooled 3-year OS of 39.5% in a recent meta-analysis. HAIP chemotherapy involves continuous administration of floxuridine (FUDR) directly into the hepatic artery using a subcutaneous pump. The aim of this study was to prospectively assess the effectiveness of HAIP with systemic chemotherapy in patients with advanced iCCA confined to the liver in the Netherlands. Methods: We performed a single arm phase II trial in 3 centers in the Netherlands. Six cycles of HAIP chemotherapy with floxuridine were scheduled with 8 cycles of concurrent systemic chemotherapy with gemcitabine and cisplatin, if not administered previously. The primary endpoint was OS, secondary endpoints were progression-free survival (PFS) and objective response. Results: From January 2020 until September 2022, 50 patients with advanced iCCA were included. Combined HAIP and systemic chemotherapy was administered to 38 patients (76.0%). Eleven patients (22.0%) received HAIP chemotherapy alone, because they had received systemic treatment before enrollment. One patient (2.0%) didn’t start treatment, because he died 19 days after pump implantation due to COVID-19. The median follow-up was 26.4 months (95% CI: 21.7 – 39.0). The median OS was 22.1 months (95% CI: 19.7 – not reached). The 1-year OS rate was 80.0% (95% CI: 69.6% – 91.9%); the 3-year OS rate was 28.6% (95% CI: 16.0% – 51.2%). The median PFS was 10.0 months (95% CI: 8.7 – 12.2). An objective response on imaging (RECIST) was achieved in 27 patients (54.0%) and disease control at 6 months in 43 patients (86.0%). Four patients (8.0%) underwent a resection after HAIP chemotherapy of whom 2 patients had a complete pathologic response. Conclusions: Combined HAIP with systemic chemotherapy for patients with advanced iCCA was associated with a favorable 3-year OS of 28.6% compared with 2.8% after systemic chemotherapy alone in the ABC trials. Clinical trial information: NL8234 .

Chemotherapy and COVID-19 Vaccination in Patients With Gastrointestinal Cancer.

Multiple doses of vaccines against the coronavirus disease (COVID-19) provide patients with cancer the opportunity to continue cancer treatment. This study investigated the safety and efficacy of COVID-19 vaccination in patients with cancer and the optimal timing of vaccination during chemotherapy. A total of 131 patients with gastrointestinal (GI) cancer who received two doses of the COVID-19 vaccine were included in this study. This study combined two cohorts: an evaluation cohort of 79 patients receiving chemotherapy and a control cohort of 52 patients under follow-up after radical surgery. None of the patients had any history of COVID-19. Treatment- and vaccine-related adverse events (AEs) were recorded through outpatient interviews and self-reports. In the evaluation cohort, 62 patients (78.4%) experienced vaccine-related AEs after the first dose, and 62 patients (78.4%) experienced vaccine-related AEs with an increased rate of fever and fatigue after the second dose. In the control cohort, vaccine-related AEs occurred in 28 (53.8%) patients after the first dose and in 37 (71.2%) patients after the second dose, with increased fever and fatigue after the second dose. Of the 79 patients, 49 received chemotherapy before vaccination. Twelve patients (24.5%) changed their treatment schedule: four for safety reasons, four for myelosuppression, and four for convenience. Three patients discontinued the treatment because of disease progression. Systemic chemotherapy in patients with GI cancer does not have a markedly negative effect on COVID-19 vaccination, resulting in manageable vaccine-related AEs, and minimizing the need for treatment schedule changes.

Combined Intraperitoneal Paclitaxel and Systemic Chemotherapy for Patients with Massive Malignant Ascites Secondary to Pancreatic Cancer: A Report of Two Patients.

The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.

Feasibility of hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for patients with colorectal liver metastases in the Netherlands: the PUMP-IT pilot study

Feasibility of hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for patients with colorectal liver metastases in the Netherlands: the PUMP-IT pilot study

Umbrella strategy with systemic and intraperitoneal chemotherapy versus systemic chemotherapy in patients with advanced gastric cancer: a multicenter, randomized Phase III clinical trial

BackgroundWe have developed a tridirectional regimen combining intraperitoneal, intravenous, and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression. This multicenter Phase III umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy.MethodsBRCA1/TOPO1 mRNA expression was examined in all enrolled patients. The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm. Patients in the control arm received systemic intravenous/oral chemotherapy, whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy. The primary endpoint was progression-free survival and the secondary endpoints were response rate, overall survival, and safety.ResultsOverall, 233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms. The objective response rate was 33.9% in the control arm and 49.1% in the individualized arm (P = 0.039). In the control and individualized arms, median progression-free survival was 5.9 months and 8.0 months, respectively (hazard ratio 0.521, 95% confidence interval 0.362–0.750, P = 0.0005) and median overall survival was 13.5 months and 16.4 months, respectively (hazard ratio 0.684, 95% confidence interval 0.474–0.988, P = 0.0430). Both regimens were tolerable.ConclusionThe primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer.Trial registrationChinese Clinical Trial Registry (chictr.org.cn) Identifier: ChiCTR-IPR-15006201.

Comparison of hepatic arterial infusion chemotherapy with mFOLFOX vs. first-line systemic chemotherapy in patients with unresectable intrahepatic cholangiocarcinoma.

Background: Systemic chemotherapy (SC) remains the only first-line treatment for unresectable intrahepatic cholangiocarcinoma (iCCA). Hepatic arterial infusion chemotherapy (HAIC) has been recently proven to be effective in managing hepatocellular carcinoma (HCC). Hence, our study aims to investigate the safety and efficacy of HAIC in treating unresectable iCCA patients. Methods: We reviewed 146 patients with unresectable iCCA who had received HAIC or SC between March 2016 and March 2022 in a retrospective manner. Outcomes of patients and safety were compared between the HAIC and SC groups. Results: There were 75 and 71 patients in the HAIC and SC groups, respectively. The median OS in the HAIC and SC groups was 18.0 and 17.8 months (p = 0.84), respectively. The median PFS in the HAIC and SC groups was 10.8 and 11.4months (p = 0.59), respectively. However, the HAIC group had significantly longer intrahepatic progression-free survival (IPFS) than the SC group (p = 0.035). The median IPFS in the HAIC and SC groups was 13.7 and 11.4months, respectively. According to the OS (p = 0.047) and PFS (p = 0.009), single-tumor patients in the HAIC group appeared to benefit more. In addition, the overall incidence of adverse events (AEs) was lower in the HAIC group than that in the SC group. Conclusion: Our study revealed that HAIC was a safe and effective therapeutic regimen for unresectable iCCA with better intrahepatic tumor control when compared to SC. Meanwhile, patients with single tumor were more likely to benefit from HAIC than SC.

ASO Visual Abstract: Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM).

ASO Visual Abstract: Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM).

Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study – (NCT05103020) – study protocol

BackgroundAlthough 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10–25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis.MethodsThis is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate.DiscussionThis is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate.Trial registrationClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.

Phase I study of intraperitoneal irinotecan combined with palliative systemic chemotherapy in patients with colorectal peritoneal metastases.

Patients with colorectal peritoneal metastases who are not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) owing to extensive peritoneal disease have a poor prognosis. It was hypothesized that these patients may benefit from the addition of intraperitoneal irinotecan to standard palliative systemic chemotherapy. This was a classical 3 + 3 phase I dose-escalation trial in patients with colorectal peritoneal metastases who were not eligible for CRS-HIPEC. Intraperitoneal irinotecan was administered every 2 weeks, concomitantly with systemic FOLFOX (5-fluorouracil, folinic acid, oxaliplatin)-bevacizumab. The primary objective was to determine the maximum tolerated dose and dose-limiting toxicities. Secondary objectives were to elucidate the systemic and intraperitoneal pharmacokinetics, safety profile, and efficacy. Eighteen patients were treated. No dose-limiting toxicities were observed with 50 mg (4 patients) and 75 mg (9 patients) intraperitoneal irinotecan. Two dose-limiting toxicities occurred with 100 mg irinotecan among five patients. The maximum tolerated dose of intraperitoneal irinotecan was established to be 75 mg, and it was well tolerated. Intraperitoneal exposure to SN-38 (active metabolite of irinotecan) was high compared with systemic exposure (median intraperitoneal area under the curve (AUC) to systemic AUC ratio 4.6). Thirteen patients had a partial radiological response and five had stable disease. Four patients showed a complete response during post-treatment diagnostic laparoscopy. Five patients underwent salvage resection or CRS-HIPEC. Median overall survival was 23.9 months. Administration of 75 mg intraperitoneal irinotecan concomitantly with systemic FOLFOX-bevacizumab was safe and well tolerated. Intraperitoneal SN-38 exposure was high and prolonged. As oncological outcomes were promising, intraperitoneal administration of irinotecan may be a good alternative to other, more invasive and costly treatment options. A phase II study is currently accruing.

Doppler Ultrasound Assessment of Tumor Vascularity in Locally Advanced Breast Cancer at Diagnosis and following Primary Systemic Chemotherapy.

The primary goal of this research is to compare the morphological response, as determined by clinical and sonographic examination, to the gold standard, histology, in assessing the effectiveness of major systemic chemotherapy in patients with locally advanced breast cancer (LABC). During the check and before each example of chemotherapy (FAC schedule), 54 patients with privately progressed, non-metastatic breast disease underwent a comprehensive clinical assessment, ultrasonography of the breast and axillae, and assortment and spooky Doppler appraisal to evaluate response to therapy. In 90% of instances, Doppler provided early insight into how a patient might respond to treatment. Disappearance of all vascular signals inside the tumor was shown to be the strongest predictor of full pathological response. Patients with LABC may benefit from using color Doppler to determine how well chemotherapy is working.

Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM)

BackgroundThis study evaluated the efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy as a bidirectional approach for gastric cancer (GC) patients with synchronous peritoneal metastases (SPM).MethodsA retrospective analysis of a prospective PIPAC database was queried for patients who underwent a bidirectional approach between October 2019 and April 2022 at two high-volume GC surgery units in Italy (Verona and Siena). Surgical and oncological outcomes were analyzed.ResultsBetween October 2019 and April 2022, 74 PIPAC procedures in 42 consecutive patients with Eastern Cooperative Oncology Group performance status ≤2 were performed—32 patients treated in Verona and 10 in Siena. Twenty-seven patients (64%) were female and median age at first PIPAC was 60.5 years (I–III quartiles: 49–68 years). Median Peritoneal Cancer Index (PCI) was 16 (I–III quartiles: 8–26) and 25 patients (59%) had at least two PIPAC procedures. Major complications according to the Common Terminology Criteria for Adverse Events (CTCAE; 3 and 4) occurred in three (4%) procedures, and, according to the Clavien–Dindo classification (>3a), one (1%) severe complication occurred. There were no reoperations or deaths within 30 days. Median overall survival (mOS) from diagnosis was 19.6 months (range 14–24), and mOS from first PIPAC was 10.5 months (range 7–13). Excluding cases with very heavy metastatic peritoneal burden, with PCI from 2 to 26, treated with more than one PIPAC, mOS from diagnosis was 22 months (range 14–39). Eleven patients (26%) underwent curative-intent surgery after a bidirectional approach. R0 was achieved in nine (82%) patients and complete pathological response was obtained in three (27%) cases.ConclusionsPatient selection is associated with bidirectional approach efficacy and feasibility for SPM GC treatment, which may allow potentially curative surgical radicalization in highly selected cases.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma

Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. ClinicalTrials.gov Identifier: NCT01946854.

Exosomal hsa-let-7g-3p and hsa-miR-10395-3p derived from peritoneal lavage predict peritoneal metastasis and the efficacy of neoadjuvant intraperitoneal and systemic chemotherapy in patients with gastric cancer.

The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients. We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells. Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance. PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance.

A prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma.

163 Background: Appendiceal adenocarcinoma is both a rare and heterogenous tumor, with marked contrast in the natural history of low-grade and high-grade tumors (5-year OS 68% for low-grade vs. 7% for high-grade). While low-grade appendiceal adenocarcinoma is primarily treated with surgical resection sometimes followed by hyperthermic intraperitoneal chemotherapy (HIPEC), many inoperable candidates are treated with systemic chemotherapy although there is no prospective data supporting this practice. The purpose of our study was to objectively evaluate the effectiveness of systemic chemotherapy in low-grade mucinous appendiceal adenocarcinoma. Methods: A randomized crossover trial of surgically unresectable low-grade (well differentiated) mucinous appendiceal adenocarcinoma was performed with patients randomized to either 6 months observation followed by 6 months of chemotherapy (physician’s choice), or initial chemotherapy followed by observation. In this way each patient would serve as their own control. Enrollment of 30 patients was planned to have complete 6- and 12-month tumor measurements for 24 patients, providing 80% power at 0.05 significance level to detect a 5.0% difference in change in tumor size as measured by peritoneal RECIST in observation vs. treatment periods. Results: The trial closed early due to slow accrual. A total of 24 patients were enrolled. The majority of patients were treated with either 5FU or capecitabine (n = 15, 63%), bevacizumab was added for 3 (13%), and 3 were treated with doublet chemotherapy (FOLFOX/FOLFIRI). 15 patients who completed both treatment and observation periods were available for the primary analysis, the mean difference in tumor size was -4.5% (95% CI: -12.6, 3.7), indicating a slight trend towards faster growth on treatment than observation. This difference was not statistically or clinically significant (8.4% growth on treatment vs. 4.0% observation, p=0.26). Of the 18 patients who received any chemotherapy during the study period, zero achieved an objective response, 14 (77.8%) had stable disease during the entire year of follow up, and 4 (12.2%) had progression on study. Patient reported quality of life metrics identified that fatigue (p=0.02), peripheral neuropathy (p=0.014), and financial difficulty (p=0.0013) were all significantly worse while on treatment. There was not a significant difference in rate of bowel obstruction between the treatment first vs. observation first arms (12.5%, (n=3) vs 8.3%, (n=2)). Conclusions: These data from a prospective, randomized crossover trial indicate that patients with low-grade mucinous appendiceal adenocarcinoma do not derive benefit from 5FU based chemotherapy but do incur toxicity. These data further highlight the unique biology of low-grade appendiceal cancer and demonstrates the need to identify novel systemic therapies for this patient population. Clinical trial information: NCT01946854 .

Impact of chemotherapy on COVID-19 vaccination in patients with gastrointestinal cancer.

32 Background: Multiple doses of vaccine against COVID-19 provide cancer patients with the opportunity to continue their cancer treatment. We previously reported the results that COVID-19 vaccination are tolerable, and treatment schedule changes could be minimized in gastrointestinal (GI) cancer patients receiving chemotherapy. In the present study, we investigated the differences in the occurrence of vaccine-related adverse events (AEs) in patients receiving chemotherapy and those not receiving chemotherapy. Methods: 141 patients with GI cancer who had two doses of mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) between May 2021 and April 2022 with sufficient data on vaccination were included in this retrospective observational study at the Tokyo Medical and Dental University hospital. This study combined two different cohorts: an evaluation cohort of 89 patients (median age 70 years, male 57.8%) receiving chemotherapy; and a control cohort of 52 patients under follow-up after radical surgery (median age 68.5 years, male 69.2%). All patients had no history of COVID-19 infection. Treatment- and vaccine-related AEs were recorded by outpatient interviews and self-reports. Results: Patient characteristics of the two cohorts were similar except for the location of primary tumor: colorectal (80.9% vs 7.7%) and gastric (15.7% vs 88.5%). There were no significant differences in comorbidities between the cohorts (67.4% vs 55.8%). In the evaluation cohorts, 65 patients (73.0%) had vaccine-related AEs: injection site pain (68.5%), fever (9.0%), fatigue (6.7%), headache (3.4%), gastrointestinal symptoms (2.2%), redness (1.1%) and sleepiness (1.1%) after the first dose; and 66 patients (74.2%) had vaccine-related AEs with increased rate of fever (32.6%) and fatigue (19.1%) after the second dose. In the control cohort, vaccine-related AEs occurred in 28 (53.8%) after the first dose and 37 (71.2%) patients after the second doses, and similarly, fever and fatigue increased after the second dose. There were no significant differences in the number of vaccine-related AEs and their changes between cohorts. There was no treatment- and vaccine-related deaths. Conclusions: The results of this study suggest that systemic chemotherapy in patients with GI cancer does not have a marked negative effect on COVID-19 vaccination.

Trends and disparities in chemotherapy utilization for metastatic hepatopancreatobiliary cancers

Background: We described trends and disparities of utilizing systemic chemotherapy in patients with metastatic hepato-pancreato-biliary (HPB) malignancies.

Trends and disparities in the utilization of systemic chemotherapy in patients with metastatic hepato-pancreato-biliary cancers

BackgroundWe described trends and disparities in utilization of systemic chemotherapy in metastatic hepato-pancreato-biliary (HPB) cancers. MethodsWe queried the National Cancer Database for metastatic HPB cancers [hepatocellular carcinoma (HCC), biliary tract cancers (BTC), pancreatic adenocarcinoma (PDAC)]. We used multivariable analysis to examine the factors associated with utilization of systemic chemotherapy. We utilized marginal structural logistic models to estimate the effect of health insurance, facility type, or facility volume on utilization of systemic chemotherapy. ResultsWe identified 162,283 patients with metastatic HPB cancers: 23,923 (14.7%) had HCC, 26,766 (16.5%) had BTC, and 111,594 (68.8%) had PDAC.A total of 37.2% patients with HCC, 55.6% with BTC, and 56.4% with PDAC received chemotherapy. Age ≥70 years and Charlson-Deyo score ≥2 were associated with lower likelihood of receiving chemotherapy across all cancers.Patients with private health insurance had higher receipt of chemotherapy. Receiving treatment at academic facilities had no effect on the receipt of chemotherapy. Treatment of patients with HCC or PDAC at high-volume facilities resulted in higher receipt of chemotherapy. ConclusionA significant proportion of patients with metastatic HPB cancers do not receive systemic chemotherapy. Several disparities in administration of chemotherapy for metastatic HPB cancers exist.

412P Phase I study of intraperitoneal irinotecan in combination with standard systemic chemotherapy in patients with extensive peritoneal metastases of colorectal origin: The INTERACT trial

The prognosis of patients diagnosed with peritoneal metastasized (PM) colorectal cancer who are ineligible for cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is poor. We hypothesize that adding intraperitoneal (IP) irinotecan to standard systemic palliative chemotherapy improves the prognosis of these patients. Therefore we conducted this phase I trial.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in multimodal therapy for patients with oligometastatic peritoneal gastric cancer: a randomized multicenter phase III trial PIPAC VEROne.

ObjectivesPeritoneal carcinomatosis is the most frequent site of metastases in patients with gastric cancer. Current standard treatment is palliative systemic chemotherapy with very poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulted in long-term benefits in selected patients. Among patients with peritoneal carcinomatosis, a distinctive subset is oligometastatic disease which is characterized by low metastatic burden. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent technique of intraperitoneal chemotherapy used in combination with systemic chemotherapy with promising results.MethodsPIPAC VER-One is a prospective, randomized, multicenter phase III clinical trial that aims to evaluate the effectiveness of the use of PIPAC in combination with systemic chemotherapy in patients with gastric cancer and synchronous positive peritoneal cytology and/or limited peritoneal metastases (peritoneal cancer index [PCI] ≤6). Patients will be randomized into two arms: arm A (control) treated with standard systemic chemotherapy and arm B (experimental) treated with a bidirectional scheme including PIPAC and systemic chemotherapy.ResultsPrimary endpoint is the secondary resectability rate. Secondary endpoints are: overall survival (OS), pregression-free survival (PFS), disease-free survival (DFS), histological response assessed both on primary tumor and peritoneal lesions, quality of life (QoL), complication rate (CTCAE v5), and incremental cost-effectiveness ratios (ICER).ConclusionsThe role of PIPAC in multimodal treatment for oligometastatic gastric cancer will be investigated in this trial.

P-247 Outcomes of randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma

Appendiceal adenocarcinoma is both a rare and heterogenous tumor, with marked contrast in the natural history of low-grade and high-grade tumors (5-year OS 68% for low-grade vs. 7% for high-grade). The rarity of appendiceal adenocarcinoma has made it difficult to study with traditional prospective, randomized controlled trials. As a result, current national guidelines still suggest that appendiceal cancer be treated similarly to colorectal cancer (CRC) despite clear differences between the two in terms of both clinical and molecular features. While low-grade appendiceal adenocarcinoma is primarily treated with surgical resection sometimes followed by hyperthermic intraperitoneal chemotherapy (HIPEC), many inoperable candidates are treated with systemic chemotherapy although there is no prospective data supporting this practice. The purpose of our study was to objectively evaluate the effectiveness of systemic chemotherapy in low-grade mucinous appendiceal adenocarcinoma. A randomized crossover trial of surgically unresectable low-grade (well differentiated) mucinous appendiceal adenocarcinoma was performed with patients randomized to either 6 months observation followed by 6 months of chemotherapy (physician’s choice), or initial chemotherapy followed by observation. In this way each patient would serve as their own control. Up to 30 patients were planned to have complete 6- and 12-month tumor measurements for 24 patients, providing 80% power at 0.05 significance level to detect a 5.0% difference in change in tumor size in observation vs. treatment periods. Patients were monitored for rate of bowel complications as a secondary endpoint for the study. The trial closed early due to slow accrual. A total of 24 patients were enrolled. The majority of patients were treated with either 5FU or capecitabine (n = 15, 63%), bevacizumab was added for 3 (13%), one patient was treated with FOLFOX, 2 (8%) were treated with FOLFIRI. Four patients did not get any chemotherapy (17%). There were 15 patients available for the primary analysis of change in tumor volume as measured by modified peritoneal RECIST. The mean difference in tumor size was -4.5 (95% CI: -12.6, 3.7), indicating a trend towards faster growth on treatment than observation, however there was no significant difference in growth of tumor during observation vs. treatment time periods (8.4% growth treatment vs. 4.0% observation, p=0.26). Separately we combined all patients with available 6- or 12-month information regardless of treatment order accounting for repeated measures again finding no significant difference (13.1% vs. 4.4%, p=0.14, n=18). There was no significant difference in overall survival between treatment first or observation first arms (76 vs. 42 months, p = 0.37). There was not a significant difference in rate of bowel obstruction between the treatment first vs. observation first arms (12.5%, (n=3) vs 8.3%, (n=2)), and no bowel perforations occurred on study. These data from a prospective, randomized crossover design trial suggest that patients with low-grade mucinous appendiceal adenocarcinoma do not appear to derive benefit from 5FU based chemotherapy. These data further highlight the unique biology of low-grade mucinous appendiceal adenocarcinomas and demonstrates the need to identify effective systemic therapies for this patient population.