Courses Of Adjuvant Chemotherapy Research Articles

Study protocol: randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs. immediate surgery and adjuvant chemotherapy for localized soft tissue sarcoma: Japan Clinical Oncology Group study JCOG2102 (NACLESS).

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30mg/m2, days 1 and 2) plus ifosfamide (2g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446).

Association of oxaliplatin-containing adjuvant duration with post-treatment fall-related injury and fracture in patients with stage III colon cancer: a population-based retrospective cohort study

PurposeOxaliplatin-containing adjuvant chemotherapy yields a significant survival benefit in stage III colon cancer and is the standard of care. Simultaneously, it causes dose-dependent peripheral neuropathy that may increase the risk of fall-related injury (FRI) such as fracture and laceration. Because these events carry significant morbidity and the global burden of colon cancer is on the rise, we examined the association between treatment with a full versus shortened course of adjuvant chemotherapy and post-treatment FRI and fracture.MethodsIn this overlap propensity score weighted, retrospective cohort study, we included patients aged ≥ 18 years with resected stage III colon cancer diagnosed 2007–2019 and treated with oxaliplatin-containing adjuvant chemotherapy (oxaliplatin plus a fluoropyrimidine; capecitabine [CAPOX] or 5-fluorouracil and leucovorin [FOLFOX]). Propensity score methods facilitate the separation of design from analysis and comparison of baseline characteristics across the weighted groups. Treatment groups were defined as 50% (4 cycles CAPOX/6 cycles FOLFOX) and > 85% (7–8 cycles CAPOX/11–12 cycles FOLFOX) of a maximal course of adjuvant chemotherapy to approximate the treatment durations received in the IDEA collaboration. The main outcomes were time to any FRI and time to fracture. We determined the subdistribution hazard ratios (sHR) estimating the association between FRI/fracture and treatment group, accounting for the competing risk of death.ResultsWe included 3,461 patients; 473 (13.7%) received 50% and 2,988 (86.3%) received > 85% of a maximal course of adjuvant therapy. For post-treatment FRI, median follow-up was 4.6 years and total follow-up was 17,968 person-years. There were 508 FRI, 301 fractures, and 692 deaths. Treatment with > 85% of a maximal course of therapy conferred a sHR of 0.84 (95% CI 0.62–1.13) for post-treatment FRI and a sHR of 0.72 (95% CI 0.49–1.06) for post-treatment fracture.ConclusionFor patients with stage III colon cancer undergoing treatment with oxaliplatin-containing adjuvant chemotherapy, any potential neuropathy associated with longer durations of treatment was not found to result in greater rates of FRI and fracture. Within the limits of this retrospective study, our findings suggest concern about FRI, while mechanistically plausible, ought not to determine treatment duration.

When synchronous mucinous metaplasia and neoplasia of the female genital tract and peutz-jeghers syndrome meet: a case report and literature reviews

BackgroundPeutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously.Case presentationWe report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment.ConclusionsThis is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians’ understanding of this disease for early detection, diagnosis and treatment.

Late coronary artery injury following chemoradiotherapy for thymic carcinoma: a case report

IntroductionSurgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients’ long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy.Case presentationThe male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components.ConclusionsChemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.

Is Prophylactic Radiotherapy to the Lymphatic Drainage Area Necessary for Patients With Stage III Ovarian Cancer After Chemotherapy Following Surgery?

For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months (P = .020), 69.2% vs 49.9% (P = .002), and 85.9% vs 50.5% (P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

The Multidisciplinary Approach to Vaginal Leiomyosarcoma, an Extremely Rare Diagnosis - Case Report

Primary vaginal sarcoma is an extremely rare malignant condition within the field of gynecological pathologies. We present the case of a 53-year old patient with no history of gynecological issues or associated comorbidities who presented to our clinic with recurrent vaginal bleeding during menopause. We want to emphasize the importance of diagnostic management, going through all the necessary steps from local gynecological examination to vaginal biopsy, optimizing results with advanced imaging techniques. Once the histopathological diagnosis of vaginal leiomyosarcoma was established, the therapeutic approach was discussed within a multidisciplinary committee consisting of a gynecologist, surgeon, and oncologist. As a result, the patient underwent tailored surgical intervention relatively quickly after presentation, followed by referral to the oncology department, where she is currently undergoing her third course of adjuvant chemotherapy. Our current objective is the long-term follow-up of the patient and the acquisition of data regarding her survival and quality of life. These facts may contribute in the future to the implementation of standardized therapeutic guidelines for such a rare condition

Postoperative Radiotherapy to Abdominal and Pelvic Lymphatic Drainage Area for Stage III Epithelial Ovarian Cancer: A Sharp Tool to Prolong Disease-Free Survival Time

For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT) after standard cytoreductive surgery (CRS) and full treatment of first-line adjuvant chemotherapy (CT). The aims of our study were to assess the therapeutic efficacy and toxicity of our special postoperative radiotherapy to abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients. We retrospectively collected patients with stage III epithelial ovarian cancer after CRS and full-course adjuvant chemotherapy. The CT+RT group patients were treated with intensity modulated radiotherapy (IMRT) to abdominal and pelvic lymphatic drainage area (which has been shown to be an alternative to whole abdominal radiotherapy (WART) both on the basis of clinical result and dosimetric verification from our prior study). The CT group data was obtained from the PUMCH's electronic medical record analytical database between 2010 and 2020. A propensity score matching analysis was performed 1:2 between CT+RT group and CT group. A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CT+RT and CT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumor, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median disease-free survival (DFS) time, 5-year overall survival (OS), and local recurrence free survival (LRFS) of CT+RT group and CT group were 100.0 months versus 25.9 months (p = 0.020), 69.2% versus 49.9% (p = 0.002), 85.9% versus 50.5% (p = 0.020), respectively. Distant metastasis was still the primary reason (57.6%), and local failure rate was 42.3%, the local recurrence rate was significantly lower in CT+RT group, compared with CT group (13.6% versus 45.5%, p = 0.016). In terms of toxicity, CT+RT group mainly presented with acute hematological toxicities, with no statistically significant difference with CT group when compared with grade III intestinal adverse effects (3/44 versus 6/88, p = 0.480). This report demonstrates that long-term disease-free survival could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to abdominal and pelvic lymphatic area. Compared with CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

Testicular metastasis 9 years after resection of primary descending colon cancer with simultaneous pulmonary metastasis: a case report

BackgroundMetastatic testicular cancer is rare. In particular, primary colorectal cancer rarely metastasizes to the testes. This study reports a case of testicular metastasis recurrence 9 years after the resection of a primary colorectal cancer and a simultaneous metastatic lung tumour.Case presentationA 69-year-old man underwent a laparoscopic left hemicolectomy for descending colon cancer. Preoperative computed tomography revealed a solitary left lung mass. Postoperative chemotherapy reduced the size of the lung mass, and 6 months after the primary resection, the patient underwent a left upper segmentectomy. Based on the pathological examination, he was diagnosed with pulmonary metastasis from colorectal cancer. After four courses of adjuvant chemotherapy, the patient was recurrence-free. However, 9 years and 6 months after the primary resection, he complained of discomfort in his left testicle. Physical examination revealed a left testicular mass. Since a malignancy was not excluded via imaging, left testicular resection was performed to confirm the diagnosis. The pathological diagnosis was testicular metastasis from colorectal cancer. The patient was followed up without medication, and remained healthy, without recurrence, 11 months postoperatively.ConclusionsIt is important to follow up with testicular metastasis in mind, although it is rare.

Effect of astragalus polysaccharides (PG2) treatment of adjuvant chemotherapy-induced fatigue in premenopausal patients with breast cancer.

537 Background: Fatigue is one of the most common symptoms of breast cancer (BC) patients who are receiving adjuvant chemotherapy. Astragalus Polysaccharides (PG2) had been proved to relieve cancer-related fatigue in advanced BC patients. The aim of this study is to evaluate the efficacy of PG2 as a complementary treatment among stage II/III BC patients with adjuvant chemotherapy of epirubicin-cyclophosphamide(EC) regimen in reduction of chemotherapy-induced toxicity and encouraging compliance with chemotherapy. Methods: This double blind, multicenter, phase II trial randomized stage II/III BC patients who would receive adjuvant EC at least 4 cycles to either PG2 500 mg or placebo on day1, 3, 8 every 21 days as the combination. Changes in chemotherapy-related fatigue score (CRFS) was evaluated by the Brief Fatigue Inventory-Taiwanese Form and incidence of Grade 3/4 neutropenia were the primary endpoints. Results: A total of 66 eligible patients were enrolled and equally randomized to PG2 and placebo groups, 30 cases in each group completed this trial. In general, there was no significant difference in the mean change of CRFS and fatigue intensity between the groups. But the CRFS and fatigue intensity in premenopausal-PG2 group were less aggravated after 4 cycles of EC than that of postmenopausal-placebo group. Persisted significance difference in CRFSs from cycle 1 day 5 (PG2: 0.6; Placebo: 1.9, P = 0.023) to cycle 4 day 15 (PG2: -0.3; Placebo: 0.7, P = 0.002). In all population, a lower proportion of patients suffered from grade 3/4 neutropenia from cycle 1 to cycle 4 were observed in the PG2 group compared to the placebo group (78.8% vs. 87.9% in intent-to-treat population). Conclusions: PG2 combined with adjuvant EC significantly improved adjuvant EC-induced fatigue in premenopausal BC patients. PG2 assists these patients with maintaining normal daily life and job activities, also less need of family support during chemotherapy. Furthermore, patients treated with PG2 might have better compliance to complete the whole course of adjuvant chemotherapy. Clinical trial information: NCT03314805 .

79P Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: An observational study with concurrent investigation of significance of TILs

Dose-dense sequential (dds) chemotherapy has tremendously changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a now widely used chemotherapeutic regimen consisting of 4 cycles of cyclophosphamide and epirubicin q2 weeks, followed by 4 cycles of docetaxel q3 weeks. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. Totally, 1,054 patients were prospectively enrolled in the current study with 1,024 patients being eligible, while adequate tissue was available for 659 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. The median DFS and overall survival (OS) had not been reached yet at the time of data cut-off for the analysis, while the 10-year DFS and OS rates were 78.4% (95% CI 75.0-81.5) and 81.7% (95% CI 79.0-84.1), respectively. The studied regimen was well tolerated with 94.7% of the patients completing the full course of adjuvant chemotherapy (8 cycles), while the rest of them discontinued the treatment, mainly due to non-fatal reasons. Only a very small percentage of patients faced clinically significant myelotoxicity. Interestingly, higher CD8+ T cells in the tumor microenvironment were associated with an improved long-term survival outcome. In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of infiltrating CD8+ lymphocytes in BC patients with early stage disease.

Primary adrenal Ewing’s sarcoma family of tumors with tumor thrombus of the inferior vena cava: a case report

BackgroundEwing’s sarcoma is a malignant neoplasm that mainly occurs in skeletal tissue but can rarely arise in soft tissues. Recently, small round cell tumors (including Ewing’s sarcoma) caused by chromosomal translocations have been collectively termed Ewing’s sarcoma family of tumors. We report a rare case of primary adrenal Ewing’s sarcoma family of tumors with tumor thrombus.Case presentationA 22-year-old Asian woman was referred to our hospital with a left retroperitoneal tumor 19 cm in diameter. Tumor thrombus was identified from the left adrenal vein to the inferior vena cava, infiltrating the right atrium. Total tumor excision with left adrenalectomy, nephrectomy, and thrombectomy was performed under hypothermic circulatory arrest, followed by seven courses of adjuvant chemotherapy. The patient has shown no signs of recurrence as of 26 months postoperatively.ConclusionRadical surgery combined with systemic chemotherapy may contribute to good prognosis in patients with primary adrenal Ewing’s sarcoma family of tumors.

JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer.

We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). The experimental treatment consisted of 3 cycles of paclitaxel (180mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1months (95% CI 6.5-11.9), while the median overall survival time was 23.2months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

Successful Combined Treatment of a Patient with Borderline Resectable Liver Metastasis of Colorectal Cancer

Aim: to present the value of interventional radiology techniques in the treatment of a patient with liver metastasis of colorectal cancer.Key points. In 2013, a 60-year-old patient with stage IIIB sigmoid colon cancer, pT3N2M0 underwent resection of the sigmoid colon with the formation of hardware rectosigmoanastomosis, 6 courses of adjuvant chemotherapy were performed. In 2015, a control examination revealed metastatic liver damage. Liver resection could not be performed due to the small future residual volume, and systemic chemotherapy was not effective. The patient underwent 3 cycles of regional chemotherapy. Taking into account the pronounced positive dynamics, in the form of a decrease in tumor size and a decrease in cancer markers, the patient managed to perform an extended right-sided hemihepatectomy. No progression of the tumor process was detected during the follow-up.Conclusion. Modern possibilities of X-ray endovascular methods allow to achieve results in the treatment of patients with colorectal cancer metastases in the liver such as a decrease in metastases in size, that make liver resection possible.

Prognostic and Predictive Significance of mRNA Expression of ABC-transporter Genes in Patients with Non-small Cell Lung Cancer

Introduction. To date, one of the reasons for the ineffectiveness of chemotherapy in various malignant neoplasms, including lung cancer, is the formation of the multidrug resistance (MDR) phenotype in tumor cells, which is caused by the expression of ABC transporter genes.Aim. The aim of this work was to assess the expression of ABC-transporter genes during chemotherapy and to analyze the relationship with the effectiveness of chemotherapy and prognosis of the disease.Materials and methods. We used biopsy and surgical material from 91 patients with stage IIB–IIIA non-small cell lung cancer (NSCLC). The treatment regimen included: 2 courses of neoadjuvant chemotherapy (NAC), surgery and 3 courses of adjuvant chemotherapy (ACT) with platinum doublets. RNA was isolated from the samples, followed by quantitative PCR to assess the expression of genes ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2.Results and discussion. It was shown that the level of expression of the studied genes was not associated with the effect of NAC in patients with lung cancer, except for the ABCC5 gene, which showed a relationship at the level of a pronounced trend (p = 0.07). It was also shown that in the group of patients with an objective response to chemotherapy, the frequency of decreased expression of the ABCC1 (p = 0.01) and ABCC5 (p = 0.004) genes was statistically significantly higher than in the group of patients with stabilization. Further, using the Kaplan – Meier method, it was found that a decrease in expression is associated with high rates of metastatic-free survival (MFS). The highest rates of 5-year MFS (more than 85 %) are observed in patients with a decrease in the expression of the ABCB1 and ABCG2 genes, log-rank test p = 0.0007 and p = 0.002, respectively.Conclusion. Thus, it has been shown that changes in the expression of ABC transporter genes are associated with the effectiveness of chemotherapy and the prognosis of the disease. The data obtained can be used as a basis for the detection of potential drug targets.

Prognostic Value of the Perioperative Systemic Inflammation Score for Patients With Curatively Resected Gastric Cancer.

The systemic inflammation score (SIS) is a promising tool for the evaluation of prognosis. The present study aimed to evaluate the clinical impact of the preoperative SIS status in gastric cancer (GC) patients who underwent curative resection. This study retrospectively analyzed 258 patients with primary gastric cancer who received curative treatment at Yokohama City University. The SIS was evaluated before surgery as determined by the lymphocyte-to-monocyte ratio (cut-off value=4.44) and serum albumin level (cut-off value=4.0 g/dl). A high SIS was identified as an independent predictor of overall survival [hazard ratio (HR)=1.784, p<0.05] and multivariate analysis showed marginal significance for recurrence-free survival (HR=1.710, p<0.05). The preoperative SIS score was correlated with both the OS and RFS of GC patients, as well as the clinical course of adjuvant chemotherapy. Thus, the SIS score is a promising prognostic factor for GC.

Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma - A Multi-Center, Randomized, Controlled Trial (pro-duct001)

Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT. We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates. Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively. This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.

The role of adjuvant treatment for early-stage uterine clear cell carcinoma (405)

<b>Objectives:</b> Uterine clear cell carcinoma (UCCC) is a rare histologic subtype of endometrial carcinoma (EC) that is associated with early metastasis, chemoresistance, and poor survival. Due to the aggressive behavior of UCCC and the inability to perform prospective clinical trials for this rare tumor type, adjuvant treatment choices for stage I and II UCCC are often made at the provider's discretion. Our objectives were to determine if adjuvant chemotherapy (CT), radiation therapy (RT), or both were associated with differences in recurrence-free survival (RFS) and overall survival (OS) in stage I and II UCCC confirmed by gynecologic pathology review. <b>Methods:</b> All patients with stage I and II UCCC between 2006 and 2019 were identified via a single institution pathology database. Electronic medical records were used for demographic and clinical- pathologic data. All cases were reviewed by a gynecologic pathologist. Cases of both pure UCCC and mixed non-serous UCCC were included due to prior evidence that mixed UCCC outcomes are driven by the clear cell (CC) component. RFS and OS were analyzed using Kaplan-Meier (KM) failure functions and a Cox proportional hazards (PH) model. <b>Results:</b> A cohort of 71 patients was identified, including 39 (55%) pure UCCC and 32 (45%) mixed UCCC. Most patients were FIGO stage IA (77.5%). Mixed UCCC tumors ranged from 2-90% CC. Among 32 patients with mixed UCCC, 30 (94%) had endometrioid/CC, and two (6%) had endometrioid, CC, and mucinous histology. Of 58 (82%) patients receiving adjuvant therapy, 43 (61%) received CT, 50 (70%) received RT, and 35 (49%) received both. Recurrences were rare, with one local, three regional, and three distant recurrences in the cohort. Deaths were also rare (<i>n</i>=9) and most likely to be cancer-related (<i>n</i>=4). The Median follow-up time was 1078 days. The 5-year RFS was 85% (95% CI: 70-93%) and 5-year OS was 88% (95% CI: 74-94%). 5-year RFS and OS among patients with and without RT were 88% (95% CI: 39-98%) versus 85% (95% CI: 71-93%) and 88% (95% CI: 62-97%) versus 87% (95% CI: 68-95%). 5-year RFS and OS among patients with and without CT were 82% (95% CI: 0.64-0.92) versus 94% (95% CI: 65-99%) and 90% (95% CI: 75-96%) versus 79% (95% CI: 32-95%). There was no difference in RFS among patients receiving no or less than six cycles of CT (<i>n</i>=38) versus patients who received six cycles (<i>n</i>=32) (HR: 0.5, 95% CI: 0.1-2.4). OS was significantly improved for patients who received six cycles of CT versus patients who received no or less than six cycles of CT (HR: 0.1, 95% CI: 0.01-0.7). On univariate analysis, receiving six cycles of CT was predictive of OS. No other variables were statistically significant; however, lymphovascular space invasion and >2 medical comorbid conditions were included in the Cox PH multivariable analysis given their clinical significance. Adjuvant CT remained a significant predictor of improved OS (HR: 0.1, 95% CI: 0.01-0.8) when controlling for these clinically significant factors. <b>Conclusions:</b> In this cohort, OS was significantly improved with six cycles of CT, and CT remained a significant predictor of OS on multivariable analysis. While additional studies are needed, our findings support a full course of adjuvant CT in patients with early-stage UCCC.

The Albumin-Bilirubin Score Is a Prognostic Factor for Gastric Cancer Patients Who Receive Curative Treatment.

The albumin-bilirubin (ALBI) score is a promising tool for the evaluation of the perioperative hepatic function. The present study aimed to evaluate the clinical impact of the preoperative ALBI status in patients with gastric cancer (GC) who received curative treatment. The present study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7849. The 3- and 5-year OS rates were 87.3% and 80.9%, respectively, in the ALBI-low group, and 66.9% and 60.6% in the ALBI-high group; these differences were statistically significant (p<0.001). The ALBI score was included in the final multivariate analysis model [Hazard ratio (HR)=2.120, 95% confidence interval (CI)=1.177-3.818, p=0.012]. Similar results were observed for RFS. In addition, the ALBI score correlated with the introduction of postoperative adjuvant chemotherapy. The preoperative ALBI score correlated with both the OS and RFS of GC patients as well as the clinical course of adjuvant chemotherapy. Taken together, the ALBI score is a promising prognostic factor for GC.

Adherence to Multidisciplinary Tumor Board Recommendations in Patients With Curable Esophageal and Gastric Cancers.

Multidisciplinary tumor board (MDT) discussion is standard practice in the management of Upper Gastrointestinal (UGI) cancers. However, poor adherence to MDT recommendations may account for the lack of improved oncological outcomes with MDTs. We aim to quantify adherence rates and compare outcomes between adherent and non-adherent patients. We included all patients with potentially curable primary UGI carcinomas who were discussed at UGI MDT from 2017 to 2018. MDT recommendations were compared to actual treatment received. Oncological and survival outcomes were compared between both groups. Amongst 153 patients, 64 (41.8%) were non-adherent to MDT recommendations. Reasons for non-adherence were patient refusal (50.0%), treatment-related complications (31.3%), disease factors (17.2%) and clinician decision (1.56%). Univariate analysis showed that non-adherent patients were older (71.6 vs 65.2years, p < 0.001), with higher clinical stage at point of diagnosis (p = 0.028), pathological stage after resection (p < 0.001) and were more likely to be recommended for multimodal therapy. No significant factors were associated with non-adherence at multivariate analysis. Non-adherent patients had worse median overall survival (19.5months) compared to adherent patients (not reached at follow-up) with both unmatched and propensity-score matched analysis. Patients who received only part of the intended adjuvant chemotherapy course had worse median overall survival and disease-free survival compared to patients who completed or did not initiate adjuvant chemotherapy. Non-adherence to MDT recommendations was associated with advanced age and tumor stage, and potentially contributes to the worse oncological outcomes in a group of patients already predisposed to poor outcomes.

Peculiarities of iron metabolism in patients with breast cancer before adjuvant chemotherapy

Introduction. Numerous studies using multivariate analysis have confirmed the relationship between low hemoglobin and / or hypoxia of tumor tissue with a worsening prognosis.The study objective was to assess the state of iron metabolism in breast cancer patients in the perioperative period, before conducting adjuvant chemotherapy for adequate administration of iron and recombinant erythropoietins preparations.Materials and methods. The object of the study included 17 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, before the first course of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25), ferritin, soluble transferrin receptors, transferin, iron, erythropoietin, C-reactive protein and interleukin 6 indicators.Results. In patients with breast cancer, even before adjuvant chemotherapy, a violation of iron metabolism was revealed. Anemic syndrome (AS) with iron deficiency erythroproiesis was diagnosed in 29.4 % of them. In most of them, AS was accompanied by a deficiency of endogenous erythropoietin. Iron deficiency anemia was more common; functional iron deficiency (FID) was found in some patients. In contrast to patients with iron deficiency anemia, patients with FID had a significant concentrations of GP25, C-reactive protein, and interleukin 6 and ferritin were within the upper limit of normal. It should be noted that GP25 hyperexression was observed not only in breast cancer patients with FID, but also in patients without laboratory signs of anemia, which did not exclude the latent stage of AS.Conclusion. To achieve the effectiveness of the treatment of AS, a comprehensive and personalized approach is required. Iron preparations are prescribed to restore iron metabolism; recombinant erythropoietins preparations are used to increase the rate of erythrocyte formation during chemotherapy. The same treatment regimen is justified for the correction of AS with FID. However, the strategy for future treatment of FID is associated with the use of GP25 antagonists (in order to overcome the retention of iron in the reticuloendothelial system), hormones or cytokines that can effectively stimulate erythropoiesis in AS with impaired iron metabolism.