Folinic Acid, Fluorouracil, And Oxaliplatin Research Articles

Identification of a Novel Protein Phosphatase 2A Activator, PPA24, as a Potential Therapeutic for FOLFOX-Resistant Colorectal Cancer.

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC50 values in the range of 2.36-6.75 μM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

The Impact of BRAF Mutation Status on Survival Outcomes and Treatment Patterns among Metastatic Colorectal Cancer Patients in Alberta, Canada.

Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation status. The Alberta Cancer Registry was used to identify all patients >18 years old who had been diagnosed with mCRC in Alberta between 1 January 2017 and 31 December 2019 and had received at least one cycle of systemic therapy. Treatment patterns were compared between wild-type and mutant BRAF mCRC patients. Cox regression models and Kaplan-Meier curves were created to assess survival differences by both treatment pattern and BRAF status. A total of 488 patients were identified with mCRC, of which 42 (11.4%) were confirmed to have a BRAF mutation. The most common first-line treatment regimen was either capecitabine and oxaliplatin (CAPOX) or leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX). The median overall survival for mCRC patients was 20.01 months. Mutant BRAF patients had a median survival of 8.21 months compared to 20.03 months among those with wild-type BRAF. BRAF mutations among mCRC patients are associated with a considerably poor prognosis, reinforcing the need for clinical BRAF testing among newly diagnosed patients to better understand their prognosis.

FOLFIRI-bevacizumab as a second-line treatment for advanced biliary tract cancer after gemcitabine-based chemotherapy.

Advanced biliary tract cancer (BTC) has a poor prognosis. Gemcitabine with platinum chemotherapy was the standard first-line chemotherapeutic regimen until the recent addition of anti-PD-1/PD-L1 antibodies. After disease progression, the only second-line chemotherapy that has demonstrated a survival benefit versus supportive care is FOLFOX (folinic acid, fluorouracil, and oxaliplatin), with a modest benefit. This study aimed to assess the efficacy and safety of second-line FOLFIRI (folinic acid, fluorouracil, and irinotecan) combined with bevacizumab for advanced BTC. This single-center retrospective study enrolled patients with metastatic BTC (intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], or gallbladder carcinoma) that progressed after first-line gemcitabine-based chemotherapy. FOLFIRI-bevacizumab was administered intravenously every 2 weeks [folinic acid 200 mg/m², fluorouracil 400 mg/m² (bolus), fluorouracil 2400 mg/m² (46-h continuous intravenous infusion), irinotecan 180 mg/m², and bevacizumab 5 mg/kg] until unacceptable toxicity, patient refusal, or disease progression. Overall, 28 patients received the FOLFIRI-bevacizumab regimen after gemcitabine-based chemotherapy. The median overall survival (OS) was 9.0 months (95% CI 6.4-16.5). The OS rate was 39.3% (95% CI 24.8-62.3) and 10.7% (95% CI 3.7-32.1) at 12- and 24-months respectively. The median progression-free survival (PFS) was 5.2 months (95% CI 3.1-10.2) with FOLFIRI-bevacizumab. The PFS rates at 12 months and 24 months were 17.9% (95% CI 8.19-39.5] and 10.7% (95% CI 3.7-31.2), respectively. The overall response rate (ORR) to FOLFIRI-bevacizumab was 23.1%, with a disease control rate (DCR) of 69.3%. Grade 3-4 adverse events (sAE) were reported in 20 patients (71.4%) treated with FOLFIRI-bevacizumab. FOLFIRI-bevacizumab as a second-line treatment for advanced BTC after gemcitabine-based chemotherapy showed efficacy and safety with a promising tumor response rate in this retrospective single-center study.

Early-stage sigmoid colon cancer resection followed by liver metastasis recurrence 1 year later and mesenteric recurrence more than 5 years later: a case report

BackgroundEarly-stage colorectal cancer (CRC) is often treated endoscopically, but additional surgical resection may be considered depending on pathological findings.Case presentationA 73-year-old man was found to have early-stage sigmoid colon cancer by colonoscopy during a medical examination, and endoscopic mucosal resection (EMR) was performed. The lesion was a 7-mm-sized sessile polyp, and the pathological diagnosis was well-differentiated tubular adenocarcinoma, pT1 (submucosal invasion of 400 μm), with no lymphovascular invasion, low budding grade, and negative horizontal and vertical margins. Therefore, the patient was observed without postoperative treatment. One year later, a computed tomography (CT) scan showed multiple liver metastases. After five courses of preoperative chemotherapy with folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and panitumumab, liver metastases were reduced. The patient underwent extended right hepatic lobectomy. The pathological finding was well-to-moderately differentiated tubular adenocarcinoma, and immunohistochemistry findings were consistent with liver metastases from sigmoid colon cancer. Postoperatively, the patient received five courses adjuvant chemotherapy with FOLFOX. Although the patient had been recurrence-free for 5 years after liver resection, a CT scan revealed a nodular lesion in the sigmoid mesentery. Positron emission tomography (PET) showed abnormal accumulation in the same lesion. Therefore, the mesenteric nodules diagnosed as lymph metastasis and recurrence of sigmoid colon cancer and performed laparoscopic sigmoid colon resection with lymph node dissection. The pathological findings showed that the recurrent lesion in the mesentery formed a nodular infiltrate with venous, lymphatic, and neural invasion, but lymph node structures were not found, and it was assumed to be metastasis or recurrence due to lymphovascular invasion. The pathologic specimen of the sigmoid colon had no neoplastic lesions, which are considered to be a local recurrence on the mucosal surface. After sigmoid colectomy, adjuvant chemotherapy with CapeOX was conducted, and the patient has been recurrence-free for 13 months at present.ConclusionEven early-stage CRCs that have no pathological indications for additional resection have risks of metastases and recurrences, and we may need to consider that the criteria for additional resection should not be limited to pathological findings alone.

Economic evaluations of radioembolization with yttrium-90 microspheres in liver metastases of colorectal cancer: a systematic review

BackgroundTransarterial radioembolization with yttrium-90 (Y-90 TARE) microspheres therapy has demonstrated positive clinical benefits for the treatment of liver metastases from colorectal cancer (lmCRC). This study aims to conduct a systematic review of the available economic evaluations of Y-90 TARE for lmCRC.MethodsEnglish and Spanish publications were identified from PubMed, Embase, Cochrane, MEDES health technology assessment agencies, and scientific congress databases published up to May 2021. The inclusion criteria considered only economic evaluations; thus, other types of studies were excluded. Purchasing-power-parity exchange rates for the year 2020 ($US PPP) were applied for cost harmonisation.ResultsFrom 423 records screened, seven economic evaluations (2 cost-analyses [CA] and 5 cost-utility-analyses [CUA]) were included (6 European and 1 USA). All included studies (n = 7) were evaluated from a payer and the social perspective (n = 1). Included studies evaluated patients with unresectable liver-predominant metastases of CRC, refractory to chemotherapy (n = 6), or chemotherapy-naïve (n = 1). Y-90 TARE was compared to best supportive care (BSC) (n = 4), an association of folinic acid, fluorouracil and oxaliplatin (FOLFOX) (n = 1), and hepatic artery infusion (HAI) (n = 2). Y-90 TARE increased life-years gained (LYG) versus BSC (1.12 and 1.35 LYG) and versus HAI (0.37 LYG). Y-90 TARE increased the quality-adjusted-life-year (QALY) versus BSC (0.81 and 0.83 QALY) and versus HAI (0.35 QALY). When considering a lifetime horizon, Y-90 TARE reported incremental cost compared to BSC (range 19,225 to 25,320 $US PPP) and versus HAI (14,307 $US PPP). Y-90 TARE reported incremental cost-utility ratios (ICURs) between 23,875 $US PPP/QALY to 31,185 $US PPP/QALY. The probability of Y-90 TARE being cost-effective at £ 30,000/QALY threshold was between 56% and 57%.ConclusionsOur review highlights that Y-90 TARE could be a cost-effective therapy either as a monotherapy or when combined with systemic therapy for treating ImCRC. However, despite the current clinical evidence on Y-90 TARE in the treatment of ImCRC, the global economic evaluation reported for Y-90 TARE in ImCRC is limited (n = 7), therefore, we recommend future economic evaluations on Y-90 TARE versus alternative options in treating ImCRC from the societal perspective.

Outcome of Operated Colorectal Cancers in Relation to the Type of Initial Referral.

Aim Since the introduction of the target referral system, there has been controversy about its value and whether it affected the short- and long-term outcomes of colorectal cancer surgeries. With contradicting results, this study highlights differences in personal and tumour characteristics, management differences, and outcomes in each referral pathway, including target pathway referrals for suspected cancers, emergency presentations, routine referrals, and incidentally discovered cancers during screening. Methods A retrospective study of colorectal cancer (CRC) patients operated on between January 1, 2010, and December 31, 2014, with records dating to the end of the five-year follow-up, was extracted anonymously from the database of CRC outcomes at the North Middlesex University Hospital NHS Trust, London. The total number of patients operated on through the four pathways was 176, with full records and competent follow-ups. Patients were classified according to the mode of referral: two-week wait (2WW or target), routine, emergency, and incidental discovery referrals. Comparisons were made between these groups with regard to personal and tumour characteristics, management, and outcome. Results It has been demonstrated by this study that targetreferrals present mainly with stage I cancers as compared to emergency referrals that present with more stage II (IIa+ IIb+ IIc). The highest percentage of cancer locations within the large bowel was rectal, followed by sigmoid in both target and emergency groups; 8.8% of target patients needed neoadjuvant chemoradiotherapy in the form of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) chemotherapy protocol with the addition of radiotherapy in patients with advanced rectal cancers, compared to 13.3% of emergency patients. Conclusion The colorectal 2WW system was the main pathway supplying colorectal cancer operations; it mostly showed earlier cancers than the other referral groups; its cancers were mostly rectosigmoid with less need for adjuvant chemotherapy; fewer recurrences; and it also showed a lower five-year mortality rate than the emergency group.

Tumor Regression Grade and Overall Survival following Gastrectomy with Preoperative Therapy for Gastric Cancer.

Pre-/perioperative chemotherapy is well-established for management of locoregional gastric cancer (LRGC). The American Joint Committee on Cancer advocates histopathologic assessment of tumor regression grade (TRG) but does not endorse a specific schema. We sought to examine the prognostic value of the recently revised National Comprehensive Cancer Network (NCCN) definition of TRG specifying TRG0 as no disease in primary tumor or lymph nodes. Patients with clinical-stage T2+/N+/M0 LRGC receiving preoperative chemotherapy and curative-intent gastrectomy were identified (2000-2020). TRG using the current NCCN definition was retrospectively assigned. Factors associated with TRG were examined using ordinal logistic regression and overall survival (OS) was assessed using the Kaplan-Meier method and Cox regression. Among 117 patients, the most common chemotherapy regimen was epirubicin, cisplatin, plus fluorouracil or capecitabine (ECF/ECX) (n = 48, 41%), followed by folinic acid, fluorouracil, and oxaliplatin (FOLFOX) (n = 30, 26%), and fluorouracil, leucovorin, oxaliplatin, plus docetaxel (FLOT) (n = 13, 11%). TRG3 was the most common histopathologic response (n = 68, 58%), followed by TRG2 (n = 25, 21%), TRG1 (n = 18, 15%), and, lastly, TRG0 (n = 6, 5.1%). The only preoperative factor independently associated with lower TRG was gastroesophageal junction tumor location (OR 0.24, p = 0.012). Higher TRG was independently associated with worse OS in a stepwise fashion (HR 1.49, p = 0.026). Posttreatment pathologic lymph node status was the strongest prognostic factor (HR 1.93, p = 0.026). Independent prognostic value of TRG and ypT stage could not be shown due to substantial overlap. TRG using the contemporary NCCN definition is associated with OS in LRGC. TRG0 is uncommon but with excellent prognosis. ypN status is the strongest prognostic factor and the revised NCCN definition acknowledging this is appropriate.

The Impact of Pre-Chemotherapy Body Composition and Immunonutritional Markers on Chemotherapy Adherence in Stage III Colorectal Cancer Patients

Patients with colorectal cancer (CRC) often fail to complete full-course chemotherapy with a standard dose due to various reasons. This study aimed to determine whether body composition affects chemotherapy adherence in patients with CRC. The medical records of 107 patients with stage III CRC who underwent adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy at a single center between 2014 and 2018 were analyzed retrospectively. Blood test results for selected immunonutritional markers were analyzed and body composition was measured through computed tomography. Univariate and multivariate analyses were performed on low and high relative dose intensity (RDI) groups, based on an RDI of 0.85. In the univariate analysis, a higher skeletal muscle index was correlated with a higher RDI (p = 0.020). Psoas muscle index was also higher in patients with high RDI than in those with low RDI (p = 0.026). Fat indices were independent of RDI. Multivariate analysis was performed for the aforementioned factors and results showed that age (p = 0.028), white blood cell count (p = 0.024), and skeletal muscle index (p = 0.025) affected RDI. In patients with stage III CRC treated with adjuvant FOLFOX chemotherapy, a decrease in RDI was related to age, white blood cell count, and skeletal muscle index. Therefore, if we adjust the drug dosage in consideration of these factors, we can expect an increased treatment efficiency in patients by increasing chemotherapy compliance.

Comparative Analysis of First-Line FOLFOX Treatment With and Without Anti-VEGF Therapy in Metastatic Colorectal Carcinoma: A Real-World Data Study.

FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) combined with or without anti-VEGF therapy represents one of the primary first-line treatment options for metastatic colorectal carcinoma (mCRC). However, there is limited comparative data on the impact of anti-VEGF therapy on treatment effectiveness, survival outcomes, and tumor location. This retrospective, comparative study utilized data from the AIM Cancer Care Quality Program and commercially insured patients treated at medical oncology clinics in the US. We analyzed 1652 mCRC patients who received FOLFOX, of which 1015 (61.4%) were also treated with anti-VEGF therapy (VEGF cohort). Patients in the VEGF cohort exhibited a higher frequency of lung (33% vs 23%; P < .001) and liver metastases (74% vs 62%; P < .001), underwent fewer liver surgeries prior to treatment (1.2% vs 3.6%; P = .002), and had a higher proportion of right-sided tumors (27% vs 18%; P = .001). Adjusted analysis revealed no significant difference in overall survival (OS) between patients treated with and without anti-VEGF (median survival: 25.4 vs 26.0 months; P = .4). FOLFOX-only treated patients experienced higher rates of post-treatment hospitalizations (22% vs 15%; P < .001). Notably, left-sided tumors treated with anti-VEGF showed a trend toward decreased OS (median survival: 26.8 vs 33months; P = .09). Our real-world data analysis suggests that the addition of anti-VEGF to FOLFOX offers limited and short-lived benefits in the context of mCRC and may provide differential survival benefit based on tumor sidedness.

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Chinese perspective.

Liver cancer is the fourth most prevalent and the second most lethal cancer in China. Hepatitis B virus (HBV) infection represents a major risk factor for hepatocellular carcinoma (HCC). Liver ultrasonography plus alpha-fetoprotein every 6 months continues to be the predominant surveillance modality. The age-Male-ALBI-Platelets score was recommended in the recent 2022 Chinese guidelines to predict HCC occurrence. The Chinese liver cancer (CNLC) staging system proposed in the 2017 guidelines continues to be the standard model for staging with modifications in the treatment allocations. Considering the aggressive nature of HBV-associated HCC, multimodal and high-intensity strategies like the addition of immunotherapy-based systemic treatment to local therapies, including resection, ablation, and intra-arterial therapies, have been adopted in real-life practices in China. The latest Chinese guidelines recommend atezolizumab plus bevacizumab, suntilimab plus a bevacizumab analog, lenvatinib, sorafenib, donafenib, and FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy as first-line treatment without priority. Regorafenib, apatinib, camrelizumab, and tislelizumab have been added as second-line systemic therapies for patients who progressed on sorafenib. Systemic therapies adopted in real-life practice are sophisticated with various combination modalities and different sequences.

Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19–14)

HER2 overexpression or amplification, which is present in 15% of all cases of biliary tract cancer, has been identified as a druggable molecular target by genomic profiling. In the phase 3 ABC-06 trial, the folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen showed a survival benefit compared with active symptom control as second-line therapy for biliary tract cancer. We aimed to evaluate the clinical activity of FOLFOX plus anti-HER2 antibody trastuzumab as a second-line or third-line treatment for HER2-positive biliary tract cancer. This study was an investigator-initiated, open-label, non-randomised, single-arm, multi institutional, phase 2 trial in participants aged 19 years or older with HER2-positive (defined as immunohistochemistry 3+ or immunohistochemistry 2+ and in-situ hybridisation positive or ERBB2 gene copy number ≥6·0 by next-generation sequencing) biliary tract cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) who progressed on chemotherapy containing gemcitabine and cisplatin (with one or two previous chemotherapy lines permitted). In cycle one, patients received intravenous trastuzumab-pkrb at 6 mg/kg on day 1, and FOLFOX (consisting of intravenous oxaliplatin [85 mg/m2], intravenous leucovorin [200 mg/m2], and fluorouracil [400 mg/m2 bolus] all on day 1, and fluorouracil [2400 mg/m2 infusion] on days 1-2. In cycle two onwards, participants were administered intravenous trastuzumab-pkrb at 4 mg/kg and FOLFOX, every 2 weeks, until unacceptable toxic effects or disease progression. The primary endpoint of the study was objective response rate based on RECIST version 1.1, assessed in the participants who completed at least one study cycle. The response rate threshold for a positive objective response rate was 25%. This trial is registered with ClinicalTrials.gov (NCT04722133) and is ongoing. 34 participants were enrolled between June 26, 2020, and Sept 1, 2021. At the time of data cutoff on May 1, 2022, median follow-up was 13·0 months (IQR 11·0-16·9), with three participants remaining on treatment. Ten patients had a partial response and 17 had stable disease; the overall response rate was 29·4% (95% CI 16·7-46·3) and the disease control rate was 79·4% (95% CI 62·9-89·9). Median progression-free survival was 5·1 months (95% CI 3·6-6·7); median overall survival was 10·7 (95%CI 7·9-not reached). The most common treatment-related grade 3 or 4 adverse events were neutropenia (ten [29%] participants with grade 3 and nine [26%] with grade 4), grade 3 anaemia (five [15%] participants), and grade 3 peripheral sensory neuropathy (four [12%] participants). There were no treatment-related cardiac toxic effects or deaths. The overall health assessment (EuroQoL-VAS) score did not change significantly throughout the treatment. Sensory and motor neuropathy symptoms as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy twenty-item scale questionnaire did not change significantly over time. For HER2-positive biliary tract cancer, second-line or third-line trastuzumab biosimilar plus FOLFOX exhibited promising activity with acceptable toxicity, warranting further investigation. Boryung Pharmaceutical, Celltrion, National Research Foundation of Korea, National R&D Program for Cancer Control through the National Cancer Center, Yonsei University College of Medicine.

Practicalities accessing precision medicine in biliary tract cancer

In The Lancet Gastroenterology & Hepatology, Choong-kun Lee and colleagues1 report the results of a single-arm, phase 2 trial assessing folinic acid, fluorouracil, and oxaliplatin (FOLFOX) and trastuzumab in patients with HER2-positive advanced biliary tract cancers pre-treated with gemcitabine and cisplatin (mostly as second-line treatment). As expected, the majority of patients had a gallbladder cancer (53%) or extrahepatic cholangiocarcinoma (29%). The trial met its primary endpoint, achieving an objective response rate of 29·4% (95% CI 16·7–46·3) that surpassed the planned 25%, and excluded the null hypothesis of 10%.

Real-world utilization and acceptance of biosimilar bevacizumab in metastatic colorectal cancer in India

Background: To describe the patient characteristics and usage pattern of biosimilar bevacizumab for the treatment of metastatic colorectal cancer (mCRC) in India.Methods: This real-world, retrospective analysis included adult patients receiving biosimilar bevacizumab between April 2021 and March 2022.Results: A total of 1125 patients with mCRC who received biosimilar bevacizumab-based chemotherapy were included. The mean age at diagnosis was 57.8 years. Majority of the patients were males (71%) and belonged to the age groups of 41-76 years. The primary tumor site was right colon (52.6%) followed by left colon (29.2%) and rectum (17.3%), and tumor grade was reported as high in most (88.7%) of the patients. Majority of the patients received biosimilar bevacizumab-based chemotherapy as first-line therapy (61.3%), followed by second-line (31.9%) and third-line therapy (6.8%). In combination with biosimilar bevacizumab, FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) was the most commonly administered chemotherapy regimen (42.9%), followed by CAPOX (capecitabine and oxaliplatin, 26.5%) and FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan, 22.8%).Conclusions: Biosimilar bevacizumab-based chemotherapy is being widely used in real‑world clinical setting in India for the management of patients with mCRC.

S3697 A Case of a Pyloric Gland Adenoma Presenting as an Intramural Mass

Introduction: Pyloric gland adenomas (PGA) are a subset of gastric adenomas with malignant potential. They are often characterized on endoscopy as an intraluminal polypoid, dome-shaped, ulcerating, or fungating mass. Due to their risk of carcinogenesis, it is important to recognize and resect lesions that are suspicious for PGAs for further pathological examination to confirm the diagnosis. Although PGAs are characterized as mucosal or submucosal lesions, this case reviews an atypical presentation of a PGA that presents intramurally in the stomach without the common features typically visualized on direct endoscopy. Case Description/Methods: A 65-year-old female with history of GERD presented with a one-year history of globus sensation described as irritation in her throat without associated weight loss, dysphagia, or odynophagia. Symptoms were refractory to proton pump inhibitors and H2 blockers. Upon initial endoscopic evaluation, a friable 3-centimeter region of localized nodular mucosa without ulceration was found on the greater curvature of the stomach and biopsied (Figure 1A). Initial pathology report noted epithelial proliferation within gastric mucosa, but malignancy was not excluded. Follow-up CT scan showed a 1.8 × 1.3 × 1.1 centimeter intramural lesion within the greater curvature at the level of the gastric fundus (Figure 1B). Upon repeat endoscopy, re-biopsy of the lesion with snare resection for more robust tissue sampling confirmed an intramucosal adenocarcinoma arising in a pyloric gland adenoma. The patient subsequently underwent a subtotal gastrectomy with Roux-en-Y gastrojejunostomy and has begun receiving adjuvant chemotherapy with folinic acid, fluorouracil and oxaliplatin (FOLFOX). Discussion: This case demonstrates the variability in presentation of PGAs while also highlighting the carcinogenic potential to evolve into an adenocarcinoma. Unlike typical PGAs that are mucosal or submucosal, this case describes an intramural PGA, which to our knowledge, has yet to be reported in the literature. Although their incidence is rare, PGAs should be considered on the differential for atypical lesions visualized on endoscopy due to their malignant potential.Figure 1.: Friable nodular ulceration on greater curvature of stomach (A), Intramural lesion within greater curvature at level of gastric fundus on CT scan (B).

Colon Cancer Pharmacogenetics: A Narrative Review.

Currently, metastatic colon cancer is treated with monotherapeutic regimens such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX), capecitabine and oxaliplatin (CapeOX), and leucovorin, fluorouracil, and irinotecan hydrochloride (FOLFIRI). Other treatments include biological therapies and immunotherapy with drugs such as bevacizumab, panitumumab, cetuximab, and pembrolizumab. After the research, it was found that some mutations make those treatments not as effective in all patients. In this bibliographic review, we investigated the pharmacogenetic explanations for how mutations in the genes coding for rat sarcoma virus (RAS) and rapidly accelerated fibrosarcoma (RAF) reduce the effectiveness of these treatments and allow the continued proliferation of tumors. Furthermore, we note that patients with mutations in the dihydropyrimidine dehydrogenase (DPDY) gene usually require lower doses of therapies such as 5-fluorouracyl (5-FU) and capecitabine to avoid severe adverse effects. Some other mutations in the thymidylate synthase gene (TSYM), methylenetetrahydrofolate reductase gene (MTHFR), and ATP binding cassette transporter B (ABCB1 and ABCB2) affect efficacy and security of the treatments. It is important to address the clinical implication of the oncologist in the study of gene mutations than can influence in the antitumoral response and safety of colon cancer treatments.

Invited Commentary: Role of the Radiologist in Pregnancy-associated Cancer.

Invited Commentary: Role of the Radiologist in Pregnancy-associated Cancer.

Dynamics of neutrophil-to-lymphocyte ratio predict outcomes of metastatic colorectal carcinoma patients treated by FOLFOX.

Peripheral blood cell count is the most common clinical laboratory test. Neutrophil-to-lymphocyte ratio (NLR) as an economic marker has been reported in various cancer types. It is believed that NLR is associated with the prognosis and treatment outcomes of some cancers. Low baseline NLR has been reported as associated with better overall survival (OS) in advanced cancer patients. In this study, we aimed to determine whether the changes of NLR may predict the outcome of metastatic colorectal carcinoma (mCRC) patients treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) combined with bevacizumab/cetuximab. The clinical data obtained from 128 mCRC patients between January 2014 and December 2018 were retrospectively analyzed. The NLR values of patients were calculated after 4 cycles of treatments. Kaplan-Meier analysis and Cox regression modeling were performed to assess the impact of NLR dynamics on OS and progression-free survival (PFS). Among the 128 participants, the optimum pre-treatment NLR cutoff value was 3. A total of 70 (54.7%) participants had a pre-treatment of NLR lower than 3. The median of PFS was 9.1 months for NLR <3 compared with 6.1 months for pre-treatment NLR >3. A lower pre-treatment NLR was significantly associated with better PFS (P<0.001), but not associated with OS (P=0.064). A total of 94 (73.4%) participants had a post-treatment NLR <3, which was associated with better PFS and OS (P=0.007). However, changes in NLR significantly affected PFS and OS. Decrease in post-treatment NLR was associated with longer PFS and OS. Patients with changes from low pre-treatment NLR to high post-treatment NLR had worse OS and PFS than that of NLR changes from high to low. It is not the NLR but the changes of NLR that may predict the efficacy of FOLFOX treatment in mCRC patients.

Effects of recombinant human adenovirus type 5 combined with transarterial chemoembolization on postoperative metastasis and recurrence of hepatocellular carcinoma patients.

Postoperative recurrence is currently the main factor affecting the long-term survival of hepatocellular carcinoma (HCC) patients. The folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen with transarterial chemoembolization (TACE) is a commonly used postoperative chemotherapy strategy, but its effect is still limited. The aim of this study was to analyze the effects of recombinant human adenovirus type 5 (rhAd5) combined with TACE on postoperative metastasis and recurrence of HCC. Patients with HCC undergoing surgical treatment were collected and divided into the rhAd5 group and control group according to whether rhAd5 was performed. The rhAd5 group was combined with rhAd5 treatment based on TACE. The recurrence and metastasis rates of the two participant groups were compared. The changes of liver function, kidney function, blood routine, and adverse reactions during treatment were analyzed. The basic data of the two groups were not significantly different (P>0.05). The recurrence and metastasis rates of rhAd5 group participants were significantly lower than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the rhAd5 group and control group (P>0.05). There were no significant differences in the incidences of adverse reactions between the rhAd5 group and control group (P>0.05). The combination of FOLFOX and rhAd5 after surgery can significantly inhibit the occurrence of metastasis and recurrence of HCC patients, improve progression free survival, and has certain safety.

Daytime versus evening infusions of immune checkpoint inhibitors.

The delivery of treatments according to circadian rhythms, known as chronotherapy, has been instrumental in the discovery of oxaliplatin efficacy and safety in colon cancer 1 Lévi F Zidani R Misset JL Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet. 1997; 350: 681-686 Summary Full Text Full Text PDF PubMed Scopus (604) Google Scholar and the efficacy of neoadjuvant chemotherapy for liver metastases from colorectal cancer in the late 1990s. 2 Giacchetti S Itzhaki M Gruia G et al. Long-term survival of patients with unresectable colorectal liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann Oncol. 1999; 10: 663-669 Summary Full Text PDF PubMed Scopus (589) Google Scholar However, no large trial has tested the chronotherapy hypothesis since 2006, when patients with metastatic colorectal cancer recruited between 1998 and 2002 given FOLFOX (a combination of folinic acid, fluorouracil, and oxaliplatin) had similar overall survival when receiving conventional or fixed-time chronomodulated therapy. 3 Giacchetti S Bjarnason G Garufi C et al. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006; 24: 3562-3569 Crossref PubMed Scopus (160) Google Scholar However, this trial showed for the first time the need for sex-specific chronotherapy schedules, with a large and significant survival benefit for chronotherapy in men, but not in women. 3 Giacchetti S Bjarnason G Garufi C et al. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006; 24: 3562-3569 Crossref PubMed Scopus (160) Google Scholar Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal studyOur findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma. Full-Text PDF

Critical reappraisal of neoadjuvant concurrent chemoradiotherapy for treatment of locally advanced colon cancer.

BackgroundLocally advanced colon cancer (LACC) is associated with surgical challenges during R0 resection, increased postoperative complications, and unfavorable treatment outcomes. Neoadjuvant concurrent chemoradiotherapy followed by surgical resection is an effective treatment strategy that can increase the complete surgical resection rate and improve the patient survival rate. This study investigated the efficacy and toxicity of concurrent chemoradiotherapy in patients with LACC as well as the prognosis and long-term clinical outcomes of these patients.MaterialsFrom January 2012 to July 2020, we retrospectively reviewed the real-world data of 75 patients with LACC who received neoadjuvant concurrent chemoradiotherapy. The chemotherapy regimen consisted of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX). The following data were obtained from medical records: patients’ characteristics, pathologic results, toxicity, and long-term oncologic outcome.ResultsOf the 75 patients, 13 (17.3%) had pathologic complete responses. Hematologic adverse effects were the most common (grade 1 anemia: 80.0% and leukopenia: 82.7%). Conversely, grade 2 or 3 adverse effects were relatively uncommon (<10%). Pathologic N downstaging, ypT0, and pathologic complete responses were significant prognostic factors for patient survival. Multivariate analysis revealed that pathologic N downstaging was an independent predictor of patients’ overall survival (P = 0.019). The estimated 5-year overall and disease-free survival rates were 68.6% and 50.6%, and the medians of overall and disease-free survival periods were 72.3 and 58.7 months, respectively. Moreover, patients with pathologic complete responses had improved overall survival (P = 0.039) and an improved local recurrence control rate (P = 0.042) but an unfavorable distant metastasis control rate (P = 0.666) in the long-term follow-up.ConclusionThe long-term oncologic outcome of patients with LACC following concurrent chemoradiotherapy is acceptable, and the adverse effects seem to be tolerable. Pathologic N downstaging was an independent prognostic factor for patients’ overall survival. However, a large prospective, randomized control study is required to confirm the current results.