Adjuvant Chemotherapy Regimens Research Articles

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-5-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled, phase 3 trial.

6000 Background: Patients with N2-3 nasopharyngeal carcinoma have a high risk of failures, despite the current practice of concurrent adjuvant cisplatin-5-fluorouracil (PF) regime. Adjuvant PF regimen may not be adequate for tumor control of high risk patients, emphasizing the need for more effective regimen of adjuvant chemotherapy in N2-3 nasopharyngeal carcinoma. Methods: We conducted this multicentre, open-label, phase 3, randomised, controlled trial in four centers in China. Patients aged 18–65 years with stage T1–4N2–3 nasopharyngeal carcinoma were randomly assigned (1:1) to receive concurrent cisplatin (100mg/m2 intravenously) on days 1, 22, and 43 of radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously on day 1) (GP) once every 3 weeks or 5-fluorouracil (4 g/m2 in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m2 on day 1 given intravenously) once every 4 weeks for three cycles. Randomisation was by a computer-generated random number code with a block size of six, stratified by treatment centre and nodal stage (N2 or N3). The primary endpoint was 3-year progression-free survival in the intention-to-treat population. This study is registered in ClinicalTrials.gov, NCT03321539. Results: From October 30, 2017 to July 9, 2020, 240 were randomly assigned to PF group (n = 120) or GP group (n = 120). After a median follow-up of 40 months (IQR: 32-48), the 3-year progression-free survival was 83.9% (95% CI 75.9–89.4) in GP group and 71.5% (62.5–78.7) in PF group (stratified HR 0.54; 95% CI, 0.32 to 0.93; p = 0.023). Significantly lower cumulative incidence of locoregional relapse (2.6% vs. 12.5%; HR 0.33; 95% CI, 0.12 to 0.90; Fine-Gray p = 0.030) and distant metastasis (10.4% vs. 20.1%; HR 0.50; 95% CI, 0.26 to 0.98; Fine-Gray p = 0.042) were also observed in GP group than PF group. However, there was no effect on early 3-year overall survival (90.7% vs. 94.0%; HR 1.12; 95% CI, 0.50 to 2.55; log-rank p = 0.779). Overall incidence of treatment-related adverse events was not significant different between the two treatment groups in the concurrent phase. In the adjuvant phase, significant higher incidence of grade 3-4 leucopenia (42 [41.2%] vs. 19 [16.8%], p < 0.001), neutropenia (33 [32.0%] vs. 10 [8.9%], p = 0.001) and thrombocytopenia (9 [8.7%] vs. 2 [1.8%], p = 0.044) was observed in GP group than PF group, whereas the frequency of diarrhea (6 [5.3%] vs. 0 [0%], p = 0.030) and mucositis (21 [18.6%] vs. 7 [6.8%], p = 0.010) was higher in PF group than in GP group. Conclusions: Concurrent adjuvant GP regimen significantly improved progression-free survival in patients with N2-3 nasopharyngeal carcinoma with acceptable toxicity. Long term follow-up is needed to confirm the ultimate therapeutic ratio. Clinical trial information: NCT03321539 .

Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US): NRG-GI008.

TPS3634 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage III A, B (all pts) and stage II, IIIC (ctDNA+ only) CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (SignateraTM, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP) + oxaliplatin (Ox) for 3-6 mos per established guidelines vs. serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs. more intensive AC with addition of irinotecan (I) for 6 mos. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs. delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022. NCT#: NCT05174169. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .

Correlation between recurrence-free survival and overall survival after upfront surgery for resected colorectal liver metastases.

The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis. Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005-2007 and 2013-2014). RFS, OS, and survival after recurrence were estimated using the Kaplan-Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated. A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06). In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.

Isolated Axillary Lymph Node Recurrence from Serous Ovarian Carcinoma: A Case Report

Ovarian cancer is the most mortal gynecological malignancy among women worldwide. The appropriate treatment protocol is cytoreductive surgery and the main aim is to remove all primary carcinoma focus and all metastatic lesions. A 37 years old woman (gravida 5, para 3) presented with complaints of abdominal distension. During the gynecological examination, bilateral adnexal masses in the solid structure were observed. Staging surgery was performed and 8 cycles of adjuvant chemotherapy regimen were given. A pathological axillary lymph node was detected in the positron emission tomography-computed tomography (PET/CT) imaging at the follow-up 6 months after the end of the chemotherapy regimen. The biopsy result from the axillary lymph node was reported as serous carcinoma metastasis. Metastasis of ovarian carcinoma to the axillary lymph node is uncommon and has a poor prognosis. High-grade ovarian serous carcinoma with axillary lymph node metastasis was presented in this case report.

N2 Lymph Node Metastasis Is a Useful Predictor of Recurrence in Patients With Stage III Rectal Cancer Undergoing Adjuvant Chemotherapy Using Tegafur-uracil/leucovorin.

Fluoropyrimidine therapy or oxaliplatin combination therapy is recommended for patients with stage III colorectal cancer as adjuvant chemotherapy (AC). However, the criterion for selecting these regimens is still unclear in patients with stage III rectal cancer (RC). In order to select an appropriate regimen of AC for such patients, it is needed to identify characteristics associated with tumor recurrence. The records of 45 patients with stage III RC undergoing AC using tegafur-uracil/leucovorin (UFT/LV) were retrospectively reviewed. The cut-off value of characteristics was determined using a receiver operating characteristic curve for recurrence. Univariate analyses using Cox-Hazard model for predicting recurrence were performed with clinical characteristics. Survival analysis was performed using Kaplan-Meier method and log-rank test. Thirty patients (66.7%) completed AC using UFT/LV. Fifteen patients (33.3%) did not complete AC because of adverse events, tumor recurrence and others. Sixteen patients (35.6%) had recurrence. Univariate analyses revealed that lymph node metastasis (N2/N1) (p=0.002) was associated with tumor recurrence. Survival analysis showed that lymph node metastasis (N2/N1) could stratify recurrence-free survival (p<0.001). N2 lymph node metastasis can predict tumor recurrence in patients with stage III RC undergoing AC using UFT/LV.

Low versus high dose of postoperative radiotherapy for locally advanced esophageal squamous cell carcinoma: a propensity score‐matched analysis

AbstractObjectiveThis study aimed to investigate the effect of different postoperative radiotherapy doses on the prognosis of patients with esophageal squamous cell carcinoma (ESCC).MethodsA total of 199 patients (aged 18–75 years) with locally advanced ESCC who underwent esophagectomy and postoperative radiotherapy/chemoradiotherapy at the Fujian Cancer Hospital between July 2008 and January 2018 were included. Based on the postoperative radiotherapy dose, the patients were divided into a low‐dose group (50–50.4 Gy; median dose 50 Gy) and a high‐dose group (&gt;50.4 Gy; median dose 60 Gy). Neoadjuvant and adjuvant chemotherapy regimens included PF (fluorouracil and cisplatin) and TP (paclitaxel and cisplatin) regimens. Patients were followed‐up every 3 months in the first 2 years after surgery, every 6 months for the next 3 years, and then subsequently once a year. The primary endpoints were overall survival (OS) and progression‐free survival (PFS) rates. The propensity‐score matching (PSM) method was applied to identify a 1:1, well‐balanced matched cohort with 33 patients in each group for survival comparison.ResultsAmong the 199 patients enrolled in this study, 144 and 55 were in the low‐dose and high‐dose groups, respectively. Univariate and multivariate analyses showed that pathological N classification, vascular tumor emboli, and postoperative radiotherapy dose were independent prognostic factors for both OS and PFS, all p &lt; 0.05. Before PSM, the OS and the PFS of the low‐dose group were significantly longer than those of the high‐dose group, both p &lt; 0.05. After PSM, better OS and PFS rates were observed in the low‐dose group, both p &lt; 0.05. The results showed that patients with pathological stages N0–2 or N3, negative surgical margins, and no vascular tumor emboli could obtain a significant benefit in both OS and PFS after treatment with a low dose of postoperative radiotherapy (50–50.4 Gy). In the subgroup with positive surgical margins, treatment with a low dose of postoperative radiotherapy offered a non‐significant survival benefit compared to treatment with a high dose of postoperative radiotherapy.ConclusionsOur study revealed that for patients with ESCC, the low‐dose group (50–50.4 Gy) had a significantly higher OS and PFS than the high‐dose group (&gt;50.4 Gy). It was suggested that 50–50.4 Gy might be the recommended postoperative radiotherapy dose for ESCC patients.

Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy.

Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial. We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival. A total of 479 patients were enrolled, with a median follow-up period of time was 36months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25-15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65-2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46-5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35-0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS. To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS.

Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer

The role of adjuvant chemotherapy in pathological T3N0M0 (pT3N0M0) gastric cancer (GC) remains unclear. The aim of this study was to analyze the prognostic factors of patients with pT3N0M0 GC and to clarify which ones could benefit from adjuvant chemotherapy. A total of 137 patients with pT3N0M0 GC were recruited between 1994 and 2020. Clinicopathological factors and adjuvant chemotherapy regimens were retrospectively collected. Prognostic factors of disease-free survival (DFS) and cancer-specific survival (CSS) were determined using univariate and multivariate analyses. The chemotherapy group was younger (p = 0.012), had had more lymph nodes retrieved (p = 0.042) and had higher percentages of vascular invasion (p = 0.021) or perineural invasion (p = 0.030) than the non-chemotherapy group. There were no significant differences in DFS (p = 0.222) and CSS (p = 0.126) between patients treated with or without adjuvant chemotherapy. Stump cancer, tumor size and perineural invasion were associated with higher rates of recurrence. Tumor size was an independent prognostic factor for DFS (hazard ratio, 4.55; confidence interval, 1.59-12.99; p = 0.005) and CSS (hazard ratio, 3.97; confidence interval, 1.38-11.43; p = 0.011). Tumor size independently influenced survival outcomes in pT3N0M0 patients who underwent radical surgery with and without adjuvant chemotherapy.

A correlation study affecting survival in patients after radical colon cancer surgery: A retrospective study.

The objective of this study was to explore the relevant factors affecting the 5-year survival rate of patients after radical colon cancer surgery, and to provide some basis for improving the quality of life and prognosis of colon cancer patients. The clinical data of 116 colon cancer patients who underwent treatment in our hospital from January 2017 to December 2017 were retrospectively selected. Using the date of performing surgical treatment as the starting point and the completion of 5 years after surgery or patient death as the end point, all patients were followed up by telephone to count the 5-year survival rate and analyze the influence of each factor with the prognosis of colon cancer patients. Of the 116 patients, 14 patients were lost to follow-up. Of the 102 patients with complete follow-up, 33 patients were died, with an overall 5-year survival rate of 67.6%. After univariate analysis, it was found that distant metastasis (χ2 = 10.493, P = .001), lymph node metastasis (χ2 = 25.145, P < .001), depth of muscle infiltration (χ2 = 14.929, P < .001), alcohol consumption (χ2 = 15.263, P < .001), and preoperative obstruction (χ2 = 9.555, P = .002) were significantly associated with the prognosis of colon cancer patients. Multivariate logistic analysis showed that distant metastasis (odds ratio [OR]: 1.932, 95% confidence intervals [CI]: 1.272-2.934, P = .002), lymph node metastasis (OR: 1.219, 95% CI: 1.091-1.362, P < .001), and obstruction (OR: 1.970, 95% CI: 1.300-2.990, P < .001) were significant independent risk factors affecting the prognosis in patients after radical colon cancer surgery. In summary, preoperative obstruction, lymph node metastasis, and distant metastasis are independent factors influencing 5-year survival rate after radical colon cancer surgery. Patients with risk factors should be followed up more closely and reasonable postoperative adjuvant chemotherapy regimens should be used to improve long-term survival.

Which selection criteria and which adjuvant chemotherapy regimen after resection of colon cancer?

Which selection criteria and which adjuvant chemotherapy regimen after resection of colon cancer?

Clinical outcomes of adjuvant taxane plus anthracycline versus taxane-based chemotherapy regimens in older adults with node-positive, triple-negative breast cancer: A SEER–Medicare study

BackgroundTriple-negative breast cancer (TNBC) is a subtype of breast cancer associated with an aggressive clinical course. Adjuvant chemotherapy reduces the risk of recurrence and improves survival in patients with node-positive TNBC. The benefit of anthracycline plus taxane (ATAX) regimens compared with non-anthracycline-containing, taxane-based regimens (TAX) in older women with node-positive TNBC is not well characterised. MethodsUsing the Surveillance, Epidemiology, and End Results–Medicare database, we identified 1106 women with node-positive TNBC diagnosed at age 66 years and older between 2010 and 2015. We compared patient clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs). Kaplan–Meier survival curves were generated to estimate 3-year overall survival (OS) and cancer-specific survival (CSS). Cox proportional hazard models were used to analyse OS and CSS while controlling for patient and tumour characteristics. ResultsOf the 1106 patients in our cohort, 767 (69.3%) received adjuvant chemotherapy with ATAX (364/767, 47.5%), TAX (297/767, 39%) or other regimens (106/767, 13.8%). Independent predictors of which patients were more likely to receive ATAX versus TAX included more extensive nodal involvement (≥4), age, marital/partner status and non-cardiac comorbidities. There was a statistically significant improvement in 3-year CSS (81.8% versus 71.4%) and OS (70.7% versus 51.3%) with the use of any chemotherapy in our cohort (P < 0.01). Three-year CSS and OS for patients who received ATAX versus TAX were similar at 82.8% versus 83.7% (P = 0.80) and 74.2% versus 72.7% (P = 0.79), respectively. There was a trend towards improved CSS and OS in patients with four or more positive lymph nodes who received ATAX versus TAX (hazard ratio 0.66, 95% CI: 0.36–1.23, P = 0.19 and hazard ratio 0.68, 95% CI: 0.41–1.14, P = 0.14, respectively). ConclusionAmong older women with node-positive TNBC, a majority of patients received adjuvant chemotherapy, which was associated with an improvement in CSS and OS. When compared with TAX chemotherapy, there was a trend towards better outcomes with ATAX for patients with ≥4 nodes.

Effect of Epirubicin Plus Paclitaxel vs Epirubicin and Cyclophosphamide Followed by Paclitaxel on Disease-Free Survival Among Patients With Operable ERBB2-Negative and Lymph Node–Positive Breast Cancer

Adjuvant therapy is an important and effective treatment for breast cancer. However, there is a lack of head-to-head clinical trials comparing the regimens epirubicin plus paclitaxel (EP) vs epirubicin and cyclophosphamide followed by paclitaxel (EC-P) in breast cancer. To evaluate the noninferiority of a cyclophosphamide-free (EP) regimen compared with the standard EC-P regimen for patients with operable hormone receptor-positive, ERBB2 (formerly HER2)-negative, lymph node-positive breast cancer. This prospective, open-label, phase 3, noninferiority randomized clinical trial was conducted from June 1, 2010, to June 30, 2016, in the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing. Patients with hormone receptor-positive, ERBB2-negative, lymph node-positive operable breast cancer were included and randomized into 2 treatment groups. Data were analyzed from June 30, 2016, to November 1, 2022. Patients received adjuvant epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for 6 cycles (EP regimen) or epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for 4 cycles followed by paclitaxel (175 mg/m2) every 3 weeks for 4 cycles (EC-P regimen) as the intention-to-treat (ITT) population. The primary outcome was disease-free survival (DFS), and the secondary outcomes included overall survival (OS), distant DFS, and safety. A total of 900 patients were registered, and 813 eligible patients (median age, 48 [IQR, 41-56] years) were randomly assigned to the EP group (n = 407) or the EC-P group (n = 406) after the surgical procedure. Through a median follow-up of 93.6 (IQR, 60.9-114.1) months, the hazard ratio (HR) of DFS for EP vs EC-P was 0.82 (95% CI, 0.62-1.10; 5-year DFS, 86.0% vs 80.6%; noninferior P = .001). The 5-year OS for the ITT population treated with the EP or the EC-P regimen was 94.7% vs 95.0%, respectively (HR, 0.95 [95% CI, 0.61-1.49]). Patients in the EP group had more frequent toxic effect events than those in the EC-P group. In this prospective, open-label, phase 3, randomized clinical trial, the EP regimen was noninferior to the EC-P regimen. These findings supported that the EP regimen could be an effective adjuvant chemotherapy regimen for women with ERBB2-negative breast cancer. ClinicalTrials.gov Identifier: NCT01134523.

Efficacy of adjuvant fluoropyrimidine with or without oxaliplatin therapy in older adults with mismatch repair deficient stage III colorectal cancer.

112 Background: Standard adjuvant chemotherapy regimens for Stage III colorectal cancer (CRC) include FOLFOX/CAPOX, 5-FU/capecitabine, or observation alone. There is uncertainty around the therapeutic benefit of adding oxaliplatin to fluorouracil in older adults over the age of 70 with Stage III CRC, including in those with mismatch repair–deficient (MMR-D) CRC. In this single institutional study, we evaluate progression free survival (PFS) across a 12-year period in patients who receive FOLFOX/CAPOX or 5-FU/capecitabine compared to active surveillance in older adults with MMR-D Stage III CRC. Methods: We identified patients diagnosed with MMR-D Stage III CRC after the age of 70 who received care at our institution and affiliates between 2005-2019. We performed a retrospective chart review of patient outcomes during the 12-year follow up period based on chemotherapy regimen to determine PFS. Patients without MMR-D staining performed at initial time of diagnosis had MMR protein immunohistochemistry performed currently and included in the analysis. Results: Among patients with MMR-D stage III CRC, 50%, 62.5%, and 76% of patients were alive at the end of year 12 with no disease progression in the observation, 5-FU/capecitabine, and FOLFOX/CAPOX groups. The PFS probabilities at one year are 69.6%, 87.5%, and 87.0%, and at five years are 41.8%, 62.5%, and 87.0% in these groups, respectively. Finally, there was a statistically significant difference (P=0.039) in PFS across all chemotherapy regimens in the MMR-D cohort. Conclusions: Based on this study, older adult patients with stage III MMR-D colorectal cancer have an improved progression free survival when treated with oxaliplatin containing chemotherapy compared to active surveillance alone. [Table: see text]

Second-line bevacizumab plus FOLFOX in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-based chemotherapy.

157 Background: There is a rarity of evidence for retreatment with oxaliplatin for metastatic colorectal cancer (mCRC), especially in combination with bevacizumab. This is a retrospective study of second line bevacizumab (Bev) plus FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-containing chemotherapy. Methods: Patients with age older than 18 and histologically confirmed metastatic colorectal cancer treated with second line bevacizumab plus FOLFOX in a single institute between 2015 and 2020 were enrolled. History of previous adjuvant chemotherapy regimens in patients with metachronous metastatic colorectal cancer was analyzed. Progression-free survival (PFS) and overall survival (OS) of the second line treatment were calculated using Kaplan-Meier method and compared between patients pretreated with adjuvant oxaliplatin (ReOx) and oxaliplatin-naive patients (control) with the log rank test. Results: A total of 72 patients were included. 23 patients (ReOx) were pretreated with adjuvant oxaliplatin and 49 patients (control) were oxaliplatin-naive before the second line treatment. There was a tendency of younger age in the ReOx group, but not statistically significant. Liver metastasis was significantly more frequent in the control group. The median PFS and OS in the ReOx group and the control group were 4.3 months (95% confidence interval [CI], 3.67–21.50) versus 5.5 months (95% CI, 4.23–8.20, hazard ratio [HR] = 0.84), and 10.5 months (95% CI, 5.40–30.37) versus 9.4 months (95% CI, 6.00–14.9, HR = 1.01) respectively. There was no significant difference of PFS ( p= 0.523) and OS ( p= 0.9745) between two groups. Conclusions: This study suggests a potential survival benefit of bevacizumab plus FOLFOX for mCRC patients previously treated with adjuvant oxaliplatin-containing treatment comparable to oxaliplatin-naive patients. [Table: see text]

NRG GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US).

TPS260 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage III A, B (all pts) and stage II, IIIC (ctDNA+ only) CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera™, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP) + oxaliplatin (Ox) for 3-6 mos per established guidelines vs . serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs . more intensive AC with addition of irinotecan (I) for 6 mos. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs . delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June, 2022. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .

Dose Delays, Dose Reductions, and Relative Total Dose Intensity in Patients With Advanced Cancer Who Exercised During Neoadjuvant Chemotherapy Treatment.

When it comes to chemotherapy, maintaining the dose and schedule of treatment are of vital importance, as clinical evidence suggests that dose intensity is associated with optimal treatment outcomes for various tumors. Yet, reduced dose intensity is a common method of mitigating the chemotherapy-induced side effects. Exercise has been shown to attenuate chemotherapy-related symptoms that frequently cluster together. Understanding this, we conducted a retrospective analysis in patients with advanced disease treated with adjuvant or neoadjuvant chemotherapy regimens and who completed exercise training during treatment. Data were collected retrospectively in a chart review of 184 patients, aged 18 years or older and treated for Stage IIIA-IV cancer. Data collection included baseline patient demographics and clinical characteristics, including age at diagnosis, cancer stage at initial diagnosis, chemotherapy regimen, and planned dose and schedule. Cancer types included brain (6.5%), breast (35.9%), colorectal (8.7%), non-Hodgkin's lymphoma (7.6%), Hodgkin's lymphoma (11.4%), non-small cell lung (16.8%), ovarian (10.9%), and pancreatic (2.2%). All patients completed at least 12 weeks of prescribed, individualized exercise. Each program included cardiovascular, resistance training, and flexibility components, under the supervision of a certified exercise oncology trainer once a week. RDI was measured for each myelosuppressive agent in a regimen over the entire chemotherapy course and then averaged across the myelosuppressive agents in a regimen. An RDI of less than 85% was designated as the clinically meaningful threshold for reduction in RDI based on previously published studies. A considerable proportion of patients across regimens had dose delays (18.3%-74.3%) and dose reductions (18.1%-84.6%). Between 12% and 83.9% of patients missed at least 1 dose of a myelosuppressive agent that was part of their standard regimen. Overall, 50.8% of patients received less than 85% of the RDI. In short, patients with advanced cancer and an exercise adherence above 84.3% saw fewer chemotherapy dose delays and dose reductions. These delays and reductions occurred significantly less frequently compared to the published norms in the sedentary population (P < .05).

Benefits of Adjuvant Chemotherapy for Clinical T3-4N0 Rectal Cancer After Preoperative Chemoradiotherapy.

While the guidelines for adjuvant chemotherapy (AC) for colon cancer are relatively standardized, those for early rectal cancer are still lacking. We therefore evaluated the role of AC in clinical stage II rectal cancer treatment after preoperative chemoradiotherapy (CRT). Patients diagnosed with early rectal cancer (defined by clinical stage T3/4, N0) who completed CRT followed by surgery were enrolled in this retrospective study. To evaluate the role of AC, we analyzed the risk of recurrence and survival based on clinicopathologic parameters and adjuvant chemotherapy. Of the 112 patients, 11 patients (9.8%) experienced recurrence and five patients (4.8%) died. In a multivariate analysis, circumferential resection margin involvement (CRM+) on magnetic resonance imaging at diagnosis, CRM involvement following neoadjuvant therapy (ypCRM+), tumor regression grade (≤G1) and no-AC were considered poor prognostic factors for recurrence free survival (RFS). In addition, ypCRM+ and no-AC were associated with poor overall survival (OS) in the multivariate analysis. AC including 5-FU monotherapy demonstrated the benefits of reduced recurrence and prolonged survival in clinical stage II rectal cancer, even in pathologic stage following neoadjuvant therapy (ypStage) 0-I. Further prospective studies are needed to verify the benefit of each regimen of AC and the development of a method that can accurately predict CRM status before surgery, and a vigorous treatment that can induce CRM non-involvement (CRM-) should be considered even in early stages of rectal cancer.

Update on management of pancreatic cancer: a literature review.

Pancreatic cancer is an aggressive malignancy with high mortality. At the time of diagnosis, majority of patients (80-90%) present with either locally advanced unresectable disease or metastatic disease. Even after curative resection, the recurrence rate remains quite high. This article aimed at reviewing the updated management of pancreatic cancer. We identified literature by searching Medline and PubMed from January 2010 to June 2023 using the keywords. A multidisciplinary approach is essential to optimize the outcomes for both curable and advanced diseases. Management of pancreatic cancer divided into resectable, borderline resectable, locally advanced, and metastatic diseases. Surgery and adjuvant chemotherapy is a standard treatment approach for resectable pancreatic cancer. The recommended adjuvant chemotherapy regimen for patients with good functional status is modified FOLFIRINOX (5-fluorouracil, folinic acid, irinotecan, and oxaliplatin). The recommended adjuvant chemotherapy regimen for patients with suboptimal functional status is gemcitabine plus capecitabine or monotherapy gemcitabine. The optimal treatment strategy for borderline resectable pancreatic cancer is still uncertain. Traditionally, upfront surgery is the choice of treatment. There is increasing evidence showing benefits of neoadjuvant therapy in borderline resectable pancreatic cancer. However, the optimal neoadjuvant treatment regimen was not certain yet. Advancement of chemotherapy has a positive impact for the survival of advanced disease. For patients with good functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is combination chemotherapy regimens such as FOLFIRINOX, gemcitabine plus nabpaclitaxel. For patients with suboptimal functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is gemcitabine plus capecitabine or monotherapy gemcitabine. Recently, more researches showed promising results in the use of nanoliposomal irinotecan, targeted agents such as a poly [adenosine diphosphate (ADB)-ribose] polymerase inhibitor, tyrosine receptor kinase (TRK) inhibitors, and immune checkpoint-inhibitors. Pancreatic cancer is a challenging disease for management. Radical surgery itself is not enough for prolong survival. The improvement of chemotherapy, target agents and immunotherapy with multidisciplinary approach will be the only solution for improvement of survival outcome and quality of life for patients with pancreatic cancer.

Primary Extrathoracic Extraskeletal Osteosarcoma of the Chest Wall: A Rare Entity

Extraskeletal osteosarcoma (ESOS) is a rapidly growing malignant neoplasm-producing osteoid, located in the soft tissues other than bones or periosteum. Primary ESOS presenting in extrathoracic locations is very rare. The optimal treatment of ESOS is largely unknown. The most common location is the soft tissues of the thigh (46%), upper extremity (20%), intrathoracic (rare), and retroperitoneum (17%). These tumors are usually large while diagnosis, typically measures 10 cm in diameter. The diagnosis is by core biopsy and microscopy sections reveal spindle cells with high NC ratio, myxoid stroma, osteoid matrix, and necrosis. Immunohistochemistry reveals that the tumor cells are positive for Desmin (40%), CD99 (25%), NKX2.2 (30%), and myogenin (15%). The radiological differentials include posttraumatic myositis ossificans. The treatment consists of wide surgical resection and reconstruction depends on the defect. Patients with localized disease were treated with an osteosarcoma-type adjuvant chemotherapy regimen consisting of doxorubicin, and cisplatin. The prognosis is poor when compared with intra-osseous osteosarcoma. More than 90% of patients develop local and distant metastasis and recurrence is between 2 months and 10 years. We hereby describe the case of giant ESOS of the chest wall, which was managed successfully at our center. A 58-year-old male presented with rapid progressive malignant ESOS in the right side chest 20 cm × 20 cm. He was managed by a multidisciplinary team of oncosurgery, plastic surgeon, and onco medicine by neoadjuvant chemotherapy and wide local excision with latissimus dorsi pedicle reconstruction. On a 3-year follow-up, he had no recurrence and doing well.

Adjuvant chemotherapy for high-grade appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

There are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort. A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables. We identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6-12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p=0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38-3.39) or without it (HR 1.33; 95%CI: 0.69-2.57), with signet ring cell (HR 0.89; 95%CI: 0.38-2.06) or other histologies (HR 1.11; 95%CI: 0.50-2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74-3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55-2.11) after adjusting for other factors. In our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.