Cycles Of Preoperative Chemotherapy Research Articles

Multidisciplinary treatment of giant thymoma, paving the way to complete surgical resection: a case report

BackgroundA multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate.Case presentationWe report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient’s age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery.ConclusionsWe report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.

Minimally invasive elective gastrectomy after preoperative chemotherapy in a patient with frailty who presented with locally far advanced-stage gastric cancer: a case report

BackgroundHerein, we report a case of gastric antrum cancer with multiple invasions to other organs that was completely cured with laparoscopic distal gastrectomy after preoperative chemotherapy in a patient with poor general condition.Case presentationAn 80-year-old male patient was diagnosed with anemia during follow-up for cerebral lacunar infarction at another hospital. He was diagnosed with advanced-stage gastric antrum cancer and was referred to our hospital. On esophagogastroduodenoscopy, type 2 advanced-stage gastric cancer was detected at the greater curvature of the antrum, and the biopsy results revealed tubular adenocarcinoma. Contrast-enhanced computed tomography scan revealed multiple invasions to other organs, thick gastric wall with contrast effect, and superior mesenteric vein tumor thrombus. However, there was no evidence of distant metastasis on positron emission tomography/computed tomography scan. The clinical diagnosis was stage IVA gastric cancer. Pancreatoduodenectomy with portal vein resection could be important at this point. However, preoperative chemotherapy with S-1 and oxaliplatin was administered instead of performing extended surgery because the patient had poor general condition (performance status score of 3). The patient received three cycles of preoperative chemotherapy at the hospital along with rehabilitation and nutritional management with oral nutritional supplements. After treatment, the performance status score of the patient improved from 3 to 1. Furthermore, in terms of clinical therapeutic effect, the patient achieved partial response. Hence, laparoscopic distal gastrectomy with D2 lymph node dissection and partial transverse colectomy was performed. After surgery, the patient was admitted for oral intake on postoperative day 6 and was discharged on postoperative day 21. Based on the histopathological examination, gastric cancer had disappeared, and there were no evident malignant findings. Therefore, gastric cancer was classified as grade 3 according to the histological treatment efficacy criteria. The patient did not present with recurrence at 2 years after surgery.ConclusionsBy actively administering preoperative chemotherapy, minimally invasive radical surgery with maximum preservation of the surrounding organs can be performed for locally far advanced-stage gastric cancer in older patients with poor general condition.

Glycemic load impacts the response of acquired resistance in breast cancer cells to chemotherapeutic drugs in vitro.

Resisting chemotherapy is a significant hurdle in treating breast cancer. Locally advanced breast cancer patients undergo four cycles of Adriamycin and Cyclophosphamide, followed by four cycles of Paclitaxel before surgery. Some patients resist this regimen, and their cancer recurred. Our study aimed to understand the underlying mechanisms of acquired resistance during these specific treatment phases. We explored how breast cancer cells, resistant to chemotherapy, respond to different glucose levels, shedding light on the intricate relationship between diabetes, breast cancer subtype, and resistance to preoperative chemotherapy. We examined two groups of cell lines: the standard MDA-MB-231 and MCF7 cells and their resistant counterparts after exposure to four cycles of Adriamycin and cyclophosphamide (4xAC) or four cycles of 4xAC and Paclitaxel (4xAC+4xPAC), aiming to unravel the mechanisms and cellular responses at these critical treatment stages. Notably, under normal and low glucose conditions, the resistant MDA-MB-231 cells showed accelerated growth compared to the control cells, while the resistant MCF7 cells proliferated more slowly than their original counterparts. Resistance to 4xAC resulted in significant cell death in both cell lines, especially under low glucose conditions, in contrast to control or 4xAC+4xPAC-resistant cells. The similarity between the MCF7 4xAC+4xPAC resistant cells and the control might be due to the P-AKT expression pattern in response to glucose levels since the levels were constant in MCF7 4xAC in all glucose concentrations. Molecular analysis revealed specific protein accumulations explaining the heightened proliferation and invasion in resistant MDA-MB-231 cells and their ability to withstand low glucose levels compared to MCF7. In conclusion, increased drug involvement corresponds to increased cell resistance, and changes in glucose levels differentially impact resistant variant cells to different drugs. The findings can be translated clinically to explain patients' differential responses to preoperative chemotherapy cycles considering their breast cancer subtype and diabetic status.

The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy.

With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers-HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren's classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.

Retroperitoneal lymph node dissection for testicular cancer is a demanding procedure: detailed real-life data of complications and additional surgical procedures in 295 cases

PurposeRetroperitoneal lymph node dissection (RPLND) for germ cell tumours is a challenging procedure that may present relevant complications. The purpose was to analyse postoperative complications and identify risk factors for major complications.MethodsThis is a retrospective unicentric analysis of a large cohort of 295 RPLNDs from 1992 to 2020. Early complications (30 days) and late complications (31–180 days) were classified according to the Clavien‒Dindo classification. The influence of surgical, patient-specific, and tumour-specific parameters on grade III–V complications was analysed in univariate and multivariate logistic regression models.ResultsA total of 232 were postchemotherapy RPLNDs, and 63 were primary RPLNDs. Early postoperative complications were found to be grades I–II in 58.6% (173/295), grades III–IV in 9.8% (29/295), and grade V in 0.3% (1/295). In 20% (58/295), additional surgical procedures were needed. Grade III–V complications were associated with ≥ 4 cycles of preoperative chemotherapy (OR 3.7 (1.5–8.9); p = 0.004), RPLND specimen (nonseminoma or immature teratoma) (OR 3.1 (1.4–6.6); p = 0.005), transfusions (OR 2.4 (1.1–5.4); p = 0.03), salvage RPLND (OR 4.1 (1.8–9.3); p < 0.001), and preoperatively elevated AFP (OR 5 (2.2–11.7); p < 0.001). In multivariate analysis, the only independent predictor for grade III–V complications was preoperative AFP elevation (OR 3.3 (1.2–9.2); p = 0.02). Limitations include the retrospective study design.ConclusionsOur results demonstrate that RPLND is a demanding surgical procedure. Patients with a complex tumour history have a higher risk of complications. We recommend treatment of these complex cases in high-volume centres.

The Role of Preoperative Chemotherapy in the Management of Synchronous Resectable Colorectal Liver Metastases: A Meta-Analysis.

The indications of preoperative chemotherapy, for initially resectable synchronous colorectal liver metastases, remain controversial. This meta-analysis aimed to assess the efficacy and safety of preoperative chemotherapy in such patients. Six retrospective studies were included in the meta-analysis with 1036 patients. Some 554 patients were allocated to the preoperative group, and 482 others were allocated to the surgery group. Major hepatectomy was more common in the preoperative group than in the surgery group (43.1% vs. 28.8%, p < 0.001). Furthermore, the percentage of patients with more than three liver metastases was higher in the preoperative group compared to the surgery group (12.6% vs. 5.4%, p < 0.002). Preoperative chemotherapy showed no statistically significant impact on overall survival. Combined disease free/relapse survival analysis of patients with high disease burden (liver metastases > 3, maximum diameter > 5 cm, clinical risk score ≥ 3) demonstrated that there is a 12% lower risk of recurrence in favor of preoperative chemotherapy. Combined analysis showed a statistically significant (77% higher probability) of postoperative morbidity in patients who received preoperative chemotherapy (p = 0.002). Preoperative chemotherapy should be suggested in patients with high disease burden. The number of cycles of preoperative chemotherapy should be low (3-4) to avoid increased postoperative morbidity. However more prospective studies are needed to clarify the exact role of preoperative chemotherapy in patients with synchronous resectable colorectal liver metastases.

A phase II study of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 followed by gastrectomy with D2 plus para-aortic nodal dissection for gastric cancer with extensive lymph node metastasis: JCOG1704.

354 Background: Prognosis of gastric cancer (GC) with extensive lymph node metastasis (ELM) is poor due to unresectability even without distant metastases. We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with docetaxel (D), oxaliplatin (O), and S-1 (S) followed by extended gastrectomy. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; bulky nodal involvement around major branched arteries to the stomach (Bulky N) and/or para-aortic nodal metastases (PAN); cM0 (except para-aortic nodes); negative lavage cytology; not linitis plastica type; PS of 0 or 1; 20-75 years old. Patients received three 21-day cycles of preoperative chemotherapy of D (40 mg/m2 on day 1), O (100 mg/m2 on day 1), and S (80-120 mg /body from day 1 to day 14), and then underwent gastrectomy with D2 plus para-aortic nodal dissection. After surgery, patients received adjuvant chemotherapy with S-1 for 1 year. Primary endpoint was major pathological response rate, defined by the disappearance of more than two-thirds of the primary tumor. Expected and threshold value of major pathological response was set at 40% and 25%, respectively. Sample size was calculated to be 50 based on a one-sided alpha of 0.1, power of 0.8 and single-arm phase II study using a Southwest Oncology Group (SWOG) two-stage design. Results: Between Oct 2018 and Mar 2022, 47 patients were enrolled, of whom 46 were eligible for efficacy analysis. The median age was 67 years. The pathological type was differentiated in 33 patients and undifferentiated in 14. Twenty patients had only bulky N, 17 had only PAN, and 10 had both of bulky N and PAN. Clinical stage was III in 19 and IV in 28 patients. Except one patient refused chemotherapy, 46 patients (45 in three cycles and 1 in one cycle) completed preoperative DOS. Forty-four patients (94%) underwent gastrectomy, including 23 distal gastrectomy and 21 total gastrectomy, and 43 (91%) had an R0 resection. Major pathological response was confirmed in 26 of 46 patients (57% with 80% CI: 46-67), including pCR of 24%, which met the statistical significance (p&lt;0.0001). According to the Becker’s criteria, grade 3 was 13, grade 2 was 12, grade 1b was 7, and grade 1a was 11. DOS-related grade 3/4 toxicities included neutropenia in 11 patients (24%), anorexia in 7 (16%), diarrhea in 4 (9%), and febrile neutropenia in 4 (9%). Surgery-related grade 3/4 toxicities were abdominal abscess in 5 (12%) and pancreatic fistula in 3 (7%). No treatment-related death was observed. Conclusions: Preoperative DOS followed by gastrectomy with D2 plus para-aortic nodal dissection is safe, feasible, and effective for GC with ELM. Clinical trial information: jRCTs031180028 .

Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases

IntroductionMany patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. MethodsWe performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the “sandwich” chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. ResultsA total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. ConclusionsIn this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study

BackgroundPreoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS.MethodsThis international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012–2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression.ResultsThe study included 423 patients who underwent pancreatectomy after a median of six (IQR 5–8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34–42 months) for BRPC and 33 months (95% CI 27–45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20–2.20) and tumor differentiation (HR 1.43; 95% CI 1.08–1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS.ConclusionsThis international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

P-256 Efficacy of FLOT regimen in the Polish population – real-world data from a prospective biomarker study

Gastric cancer is associated with poor prognosis. Currently in Europe the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer is perioperative chemotherapy using FLOT regimen. According to previously published data, such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. It was an academic, nonrandomized, prospective study, conducted in Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019 we analysed a total of 61 patients aged 30-77 (median 63 years, 52.5% male and 47.5% female) with histologically confirmed GC or GEJ cancer. The patients were qualified by multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analysed. All patients received G-CSF prophylactically. After gastrectomy, assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anaemia (64% vs 62%) nausea (60% vs 60%), peripheral neuropathy (60% vs 60%) and oral mucositis (59% vs 50%), respectively. Only 24.6% (15) had any G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated disease-free survival (DFS) at 3 years was 53% (95% CI 40.5%-66.1%) and estimated overall survival (OS) at 3-years was 60.2% (95% CI 45.1%-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients’ prognosis with acceptable side-effect profiles.

Individualized Treatment for Advanced Non-Small Cell Lung Cancer: A Case Report and Literature Review.

The incidence of lung cancer is high and about 75% of the patients with lung cancer are found in the middle and advanced stage, which has a limited treatment strategy. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. In this article, we delineate the treatment process of a middle-aged male patient with advanced-stage lung cancer to explain the significance of individualized chemotherapy combined with immunotherapy and surgery. This patient has extensive bone metastasis with PS scores of 2. After nine cycles of preoperative neoadjuvant chemotherapy, surgery, and two cycles of postoperative adjuvant chemotherapy, the patient achieved complete response (CR) and his PS score was 0. Although there is a standard chemotherapy regimen for lung adenocarcinoma, the treatment effect varies because of individual differences. Comprehensive analysis of the characteristics of patients through a variety of means to develop a precise individualized chemotherapy plan will be a major direction of lung cancer treatment in the future. Additionally, surgical treatment for advanced lung cancer patients after chemotherapy can effectively reduce the primary lesion and prolong the survival time of patients.

209: ROLE OF ADJUVANT CHEMOTHERAPY IN LOW BURDEN (YPT0-T1N0) GASTRIC ADENOCARCINOMA AFTER NEOADJUVANT CHEMOTHERAPY

Abstract Background and aim Since 2006, perioperative chemotherapy(periCT) has become an established treatment for patients with resectable gastric adenocarcinoma in Europe after the demonstration of a survival benefit in two randomized clinical trials. However, only half of patients included in the periCT arm started adjuvant chemotherapy(adjCT), suggesting a preponderant effect of neoadjuvant chemotherapy(neoCT) on the survival benefit observed. The aim of this study was to assess the benefit of adjCT on disease-free survival in patients with low tumor burden(LTB) (ypT0N0 or ypT1N0) after neoCT. Methods Data were collected from 30 European centres from 2007 to 2017. Among 2131 included patients, 762 patients received neoCT and 135 had LTB (17.7%), including 40 patients (5.3%) with complete pathological response. Among patients with LTB, 85 (63%) received adjCT(adjCT+) and 50 patients (37%) did not (adjCT-). Propensity score matching analyses were used to compensate for differences in baseline characteristics between ajdCT+ and adjCT- patients. Results NeoCT regimen was mainly based on platinum-fluoropyrimidine doublet or triplet regimen(88.1%). In univariate analysis, predictive factors for LTB after neoCT were antro-pyloric location, pretherapeutic stage≤cT2, well-differentiated tumor, ≥2 cycles of preoperative chemotherapy, intestinal or mixt-type according to Lauren’s classification and non poorly-cohesive cells tumor. Patients in adjCT- group were older and had more frequently severe postoperative complications (≥ grade 3a according to Dindo-Clavien’s classification) than patients in adjCT+ group. Despite this, 5-years overall(OS) and disease-free survival(DFS) rates were comparable between adjCT+ and adjcCT- groups, respectively 92% vs. 82% and 89% vs.83%. After propensity score analysis, OS and DFS remain comparable between adjCT+ and adjCT- groups. In adjCT+ group, patients received mostly the same chemotherapy as that received preoperatively (82%). However, severe toxicity was described in 11 patients (13%). Among patients with ypT0N0 response with a follow-up longer than 3 months, 4 patients experienced tumor recurrence or death (11.4%). All of these patients had received adjuvant chemotherapy. Conclusion Performing adjCT in patients with LTB after neoCT does not seem to provide any benefit on OS or DFS, with non-negligible toxicity rates in counterpart.

Predictive value of serum alpha-fetoprotein for tumor regression after preoperative chemotherapy for rectal cancer.

BACKGROUNDPreoperative therapy is widely used in locally advanced rectal cancer. It can improve local control of rectal cancer. However, there are few indicators that can predict the effect of preoperative chemotherapy accurately.AIMTo investigate whether the increase in serum α-fetoprotein (AFP) can predict better efficacy of preoperative chemotherapy.METHODSThis was a retrospective study. We analyzed 125 patients admitted between 2017 and 2019 with locally advanced rectal cancer. All patients received six cycles of preoperative chemotherapy (mFOLFOX6 every 2 wk). Serum AFP of 26 patients rose slightly after three or four cycles of chemotherapy, and fell to normal again within 2 mo. The other 99 patients had a normal level of serum AFP during chemotherapy. Patients were divided into two groups (AFP risen and AFP normal). According to postoperative pathology, we compared tumor regression and complete response rate between the two groups. The primary outcome measure was the tumor regression grade (TRG) after chemotherapy. The difference in pathological complete response between the two groups was also investigated.RESULTSThere were no tumor progression and distant metastasis in both groups during preoperative chemotherapy. Patients in the AFP risen group achieved better TRG 0/1 than those in the AFP normal group (61.5% vs 39.4%). The increase in AFP was a significant predictor for better tumor regression [χ2 = 4.144, odds ratio (OR) = 2.666, P = 0.04]. In the AFP risen group, the complete response rate was 30.8%, which was higher than in the AFP normal group (30.8% vs 12.1%, χ2 = 4.542, OR = 3.251, P = 0.03).CONCLUSIONPatients with a slight increase in serum AFP can achieve better tumor regression during preoperative chemotherapy, and are more likely to achieve pathological complete response.

Short-term outcomes of preoperative chemotherapy in patients with upper ampullary rectal cancer

The purpose of the study: to analyze short-term efficacy and tolerability of preoperative chemotherapy in patients with upper ampullary rectal carcinoma. Material and methods. A prospective study conducted at the cancer research institute (tomsk, russia) between 2018 and 2020 included 47 patients with operable cancer of the upper ampullary part of the rectum with mrt3n0m0 (mesorectal fascia involvement (crm+) or low-grade cancer), mrt4аn0m0 and mrt3–4аn1m0. All patients were divided into two groups. Group i comprised 22 patients, who received 3 cycles of chemotherapy with folfox-4 followed by surgery. Group ii consisted of 25 patients, who underwent surgery alone. All patients underwent arterior resection of the rectum. Results. Group i patients completed all three cycles of preoperative chemotherapy. Downstaging after chemotherapy was observed in 16 (72.7 %) patients. No severe side effects of chemotherapy were found. The frequency of radical surgeries (r0) was 100 %. No significant differences in the rate of postoperative complications between the treatment groups were observed (18.2 % and 16 %, respectively, p&gt;0.05). There were no cases of postoperative mortality. Conclusion. Compared with surgery alone, preoperative chemotherapy followed by surgery demonstrates a high short-term efficacy, does not adversely affect the course of the perioperative period.

Safety and efficacy of the FLOT regimen in the Polish population - an analysis of the prospective trial.

As gastric cancer is associated with poor prognosis, the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in European patients is perioperative chemotherapy using the FLOT regimen. Previously published data demonstrate that such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. In order to collect biomaterial for the identification of serum biomarkers of an early response to neoadjuvant chemotherapy, we performed a prospective study and here, we report the safety and clinical efficacy of this prospective cohort. It was an academic, nonrandomized, prospective study, conducted at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019, we analyzed a total of 61 patients aged 30-77 (median 63 years, 52.5% males and 47.5% females) with histologically confirmed GC or GEJ cancer. The patients were qualified by a multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analyzed. All patients received G-CSF prophylactically. After gastrectomy, an assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anemia (64% vs. 62%), nausea (60% vs. 60%), peripheral neuropathy (60% vs. 60%), and oral mucositis (59% vs. 50%), respectively. Only 24.6% (15) had G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated DFS at 3 years was 53% (95% CI 40.5-66.1%) and the estimated OS at 3 years was 60.2% (95% CI 45.1-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients' prognosis with acceptable side-effect profiles.

Neither Surgical Margin Status nor Somatic Mutation Predicts Local Recurrence After R0-intent Resection for Colorectal Liver Metastases

BackgroundWe evaluated the associations of surgical margin status and somatic mutations with the incidence of local recurrence (LR) and oncologic outcomes in patients undergoing R0-intent (microscopically negative margin) resection of colorectal liver metastases (CLM). MethodsPatients with CLM who underwent initial R0-intent resection and analysis of tumor tissue using next-generation sequencing during 2001–2018 were analyzed. Recurrences were classified as LR (at the resection margin), other intrahepatic recurrence, or extrahepatic recurrence. Predictors and survival effect of LR were evaluated using univariate and multivariate analysis. ResultsOf 552 patients analyzed, 415 (75%) had R0 resection (margin width ≥ 1.0 mm), and 38 (7%) had LR. LR incidence was not affected by surgical margin width. RAS/TP53 co-mutation was associated with increased risk of intrahepatic recurrence (67% vs. 49%; p < 0.001) and overall recurrence (p < 0.001). However, incidence of LR did not differ significantly by RAS/TP53, BRAF, SMAD4, or FBXW7 mutation. Extrahepatic disease (hazard ratio [HR], 1.47; p = 0.034), > 8 cycles of preoperative chemotherapy (HR, 1.98; p = 0.033), tumor viability ≥ 50% (HR, 1.55; p = 0.007), RAS/TP53 co-mutation (HR, 1.69; p = 0.001), and SMAD4 mutation (HR, 2.44; p < 0.001) were independently associated with poor overall survival, but surgical margin status was not. ConclusionsAlthough somatic mutations were associated with overall recurrence, neither surgical margin width nor somatic mutations affected LR risk after R0-intent hepatectomy for CLM. LR and prognosis were likely driven by individual tumor biology rather than surgical margins.

Repeat hepatectomy for recurrent colorectal liver metastases: A comparative analysis of short- and long-term results

BackgroundLiver recurrence after resection of colorectal liver metastases (CRLM) is frequent. Repeat hepatectomy has been shown to have satisfactory perioperative results. However, the long-term outcomes and the benefits for patients with early recurrence have not been clarified. The aim of this study was to compare the short- and long-term outcomes of patients undergoing single hepatectomy and repeat hepatectomy for CRLM. Additionally, the oncological outcomes of patients with early (≤ 6 months) and late recurrence who underwent repeat hepatectomy were compared. MethodsConsecutive adult patients undergoing hepatectomy for CRLM between June 2000 and February 2020 were included and divided into two groups: single hepatectomy and repeat hepatectomy. ResultsA total of 709 patients were included: 649 in the single hepatectomy group and 60 in the repeat hepatectomy group. Patients in the repeat hepatectomy group underwent more cycles of preoperative chemotherapy [4 (3-6) vs. 3 (2-4), P = 0.003]. Patients in the single hepatectomy group more frequently underwent major hepatectomies (34.5% vs. 16.7%, P = 0.004) and had a greater number of lesions resected (2.9 ± 3.6 vs. 1.9 ± 1.8, P = 0.011). There was no increase in operative time, estimated blood loss, length of hospital stay, complications, or mortality in the repeat hepatectomy group. There were no differences in overall survival (P = 0.626) and disease-free survival (P = 0.579) between the two groups. Similarly, for patients underwent repeat hepatectomy, no difference was observed between the early and late recurrence groups in terms of overall survival (P = 0.771) or disease-free survival (P = 0.350). ConclusionsRepeat hepatectomy is feasible and safe, with similar short- and long-term outcomes when compared to single hepatectomy. Surgical treatment of early liver recurrence offers similar oncological outcomes to those obtained for late recurrence.

Perioperative chemotherapy in locally advanced gastric cancer in Chile: from evidence to daily practice.

Gastric cancer (GC) is a leading cause of cancer death in Chile. Although recommended in international guidelines since 2006, perioperative chemotherapy was not available to patients in the public health system in Chile until 2016. We conducted an observational study to assess the feasibility of this strategy in public hospitals in Chile (Observational Study of Perioperative Chemotherapy in Locally Advanced Gastric Cancer – PRECISO). Patients with locally advanced, operable GC were offered to receive preoperative chemotherapy with Epirubicin + Cisplatin + Capecitabine (ECX) for three cycles followed by curative surgery. Staging included abdominal CT scan and laparoscopy if peritoneal carcinomatosis was suspected. Postoperative ECX for three cycles was recommended. Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23–76 years) and most patients had good performance status at baseline (Eastern Cooperative Oncology Group performance status score (ECOG) 0: 42, ECOG 1: 19). Tumour site was proximal in 32 (52%) and medial and distal in 29 (48%) patients. All but four patients (n = 57, 93%) completed three cycles of preoperative chemotherapy. Fifty-six patients were operated and 54 (89%) had a curative resection. Thirty-three patients (54%) had pT0-2, and 18 (30%) had pN0 tumours, with two patients achieving a complete response. As of 20 December 2020, 39 patients died, 32 due to GC, one within 30 days of surgery, two due to intestinal obstruction at 5 and 3 months after surgery and four due to other causes. Five-year survival rate was 38%. We conclude that perioperative chemotherapy is feasible in public hospitals in Chile and should be offered to patients with locally advanced GC.

INNOVA: Interval or neoadjuvant chemotherapy in rectal cancer—A phase II randomized study comparing interval versus neoadjuvant chemotherapy in magnetic resonance imaging-defined high-risk rectal cancer.

91 Background: Total neoadjuvant treatment is a promising option in rectal cancer. We aim to compare neoadjuvant versus interval chemotherapy in high risk rectal cancer to identify the optimal sequencing of treatment. Methods: Using a Simon two-stage design, newly diagnosed MRI defined high risk rectal cancer patients were randomly assigned in a 1:1 ratio to receive three 21 day cycles of chemotherapy with Capecitabine 1000 mg/m2 and Oxaliplatin 130 mg/m2 either before (Arm A-neoadjuvant) or after (Arm B-interval) chemoradiation followed by surgery. Primary end point was the pathological complete response (pCR) following surgery. A heirarchial model was used to assess the primary and secondary end points (toxicity and compliance) and compare the two regimens. (Clinical Trial Registry of India No. CTRI/2015/01/005385). Results: In this single centre study conducted between November 2015 and February 2020, 42 patients were randomised in the first stage. A pCR was seen in 4 patients in Arm A and 6 in Arm B. Hence another 52 patients were randomised in the second stage of which an additional 3 and 2 patients had a pCR leading to an overall pCR of 7 and 8 patients (15.5% vs 17% and 18.4% vs 19.5% in the intent-to-treat and per-protocol populations in Arm A and B respectively. This exceeded the minimum predetermined number of 5 pCR needed to qualify for further evaluation for each arm. Grade ≥3 toxicity was observed in 2.2% of 132 cycles and 4.6% of 129 cycles of chemotherapy delivered in 45 and 43 patients in Arm A and B respectively while 11/43 (25.5%) and 10/47 (21.2%) patients experienced grade ≥3 toxicity during chemoradiation. Treatment break of &gt; 7 days was seen in 23.2% and 29.7% of patients in Arm A and B respectively while 93.3% in Arm A and 100% of patients in Arm B completed all 3 planned cycles of pre-operative chemotherapy. A non-significant trend towards greater pathological downstaging was seen in Arm B than in Arm A (ypT1-2 39% vs 26.3%; p = 0.1 and ypN0 68.3% vs 57.9%; p = 0.5 respectively). Conclusions: In this phase two study, both neoadjuvant and interval chemotherapy emerged eligible for further evaluation against the standard of care in a future phase III study. Although we could not pick one winner based on pCR, toxicity or compliance, the greater downstaging observed with interval chemotherapy suggests it could play a greater role in an organ preservation approach. Clinical trial information:CTRI/2015/01/005385, UTN no: U111111650578.

Indocyanine green fluorescence guided laparoscopic hepatectomy of segment VI for metachronous colorectal liver metastases in a severely obese patient

Purpose: Liver resections in severely obese patients (BMI > 35) are related with increased post-operative morbidity. The use of the laparoscopic approach is associated with fewer complications vs open approach. Indocyanine green (ICG) fluorescence has been recently used for tumour identification in laparoscopic liver resections. We describe a total laparoscopic hepatectomy of segment VI using ICG fluorescence guided technique in a severely obese patient. Method: 68 years old male patient was referred to our unit for management of metachronous liver metastases of segment VI. He had undergone open sigmoidectomy three years ago for a pT4aN2a sigmoid adenocarcinoma. Upon diagnosing metachronous metastatic liver disease, five cycles of preoperative chemotherapy were administered with a good response, as reflected by Carcinoembryonic antigen values and radiological assessment (PET-CT and CT abdo). The patient was severely obese (BMI:37) with a post-operative midline hernia. A laparoscopic approach was decided. Material: ICG (2,5 mg) was administered intravenously 24 hrs prior to surgery. In theatre, the patient was placed in a left lateral decubitus position. Initially, an intraoperative U/S was performed. Total laparoscopic resection of segment VI was performed. Liver transection was performed using laparoscopic Cusa, harmonic scalpel, and intermittent Pringle manoeuvre application. Liver resection with clear macroscopically margins was facilitated significantly by ICG fluorescence image-guided for tumour identification. The specimen was removed through the previous midline incision, and the incisional hernia was corrected. The post-operative course was uneventful, and the patient was discharged on the 4th post-operative day. Histopathology confirmed the presence of metastatic colon adenocarcinoma with clear resection margins (R0 resection). Conclusion: The use of image-guided techniques, for intra-operative tumour identification, facilitates the safe performance of laparoscopic liver resections in severely obese patients with good post-operative outcome.