Months Of Adjuvant Chemotherapy Research Articles

Adjuvant Chemotherapy After Neoadjuvant Chemotherapy for Pancreatic Cancer is Associated with Improved Survival for Patients with Low-Risk Pathology.

With limited evidence, the benefit of adjuvant chemotherapy (AT) after completion of neoadjuvant chemotherapy (NT) and surgical resection for patients with pancreatic adenocarcinoma is debated. Guidelines recommend 6 months of AT for patients receiving NT. However, the patient-derived benefit from additional AT remains unknown. The National Cancer Database from 2006 to 2015 was used to identify patients undergoing NT. The chi-square test and multivariable logistic regression were used to identify differences between those receiving only NT and those receiving NT and AT. Survival analysis using the Kaplan-Meier method and the Cox proportional hazard ratio model was applied to the entire cohort and to subgroups with differing lymph node ratios (LNRs), tumor sizes, grades, and surgical margin statuses. Of the 3897 patients who received NT, 36.7 % received additional AT. Analysis of the entire cohort showed that associated survival was significantly improved with NT and AT compared with NT alone (hazard ratio [HR], 0.83; p < 0.001). In the subgroup analysis, the survival benefit of additional AT remained significant for those with negative nodal disease, an LNR lower than 0.15, low-grade histology, and negative margin status. Overall survival did not differ between those receiving NT only and those receiving NT and AT in the group with an LNR of 0.15 or higher, high-grade histology, and positive margins. This study identified an increasing trend in the use of AT after NT and showed an associated survival benefit for subgroups with low-risk pathologic features. These results suggest that the addition of AT after NT likely beneficial for these subgroups.

Clinicopathological characteristics and impact on efficacy of three versus six months of adjuvant chemotherapy in early-onset colon cancer: ACHIEVE and ACHIEVE-2 trials.

60 Background: Colorectal cancer (CRC) incidence and mortality have decreased since the 1970s but several data such as the SEER CRC registry show that the incidence of early onset colon cancer (eoCC, age 20-49) and RC keep increasing. There is limited results suggesting eoCC may have different behaviors compared to traditional CC (tCC, age ≥ 50). Methods: Individual patient data of 1,805 high-risk stage II/III colon cancer (CC) patients (pts) as the modified ITT population in ACHIEVE and ACHIEVE-2 trials were investigated. Clinicopathological features and treatment-related data were assessed by age group. Disease-free survival (DFS) was assessed by Kaplan-Meier curves and Cox multivariable models adjusted by trials, regimen, T and N. Results: Of the 1,805 pts, eoCC were 155 pts (8.6%). Using 5% difference between age groups as clinically meaningful cutoff, eoCC had similar gender (female, 52 vs 48%), PS (PS = 1, 1 vs 4%), risk group (high-risk, 43 vs 42%) and T stage (T4, 30 vs 30%) as tCC, while eoCC were less likely right-sided colon primary (32 vs 39%), had N1 disease (48 vs 54%), and treated by FOLFOX (16 vs 23%). Overall, eoCC significantly had a worse DFS than tCC (3y-DFS, 75 vs 82%; Adjusted Hazard Ratio = 1.40: 95% Confidence Interval, 1.00-1.95: p= 0.0478); in addition, similar DFS were observed among tCC pts (age 50-69 vs &gt;70). eoCC experienced less neutropenia, thrombocytopenia and stomatitis, but had more diarrhea, nausea and/or vomiting. There were 38 and 297 pts with an initial relapse in eoCC and tCC, respectively. Of those, peritoneal metastases were more frequently seen in eoCC (n = 13, 34%) than in tCC (n = 63, 21%) (p = 0.097), whereas liver and lung metastases were similar between the two groups. Impact on DFS of 3 versus 6 months of adjuvant chemotherapy in eoCC (3y-DFS, 75% vs 76%) is similar to that in tCC (83% vs 81%). Conclusions: eoCC had unique characteristics; the difference in DFS between eoCC and tCC were potentially due to a different metastatic spread. eoCC had a different adverse event profile compared to tCC. No impact on DFS of treatment duration in eoCC was suggested. Clinical trial information: UMIN000013036.

Duration of adjuvant treatment for patients with stage III colon cancer.

In The Lancet Oncology, Thierry André and colleagues1 present data on 5-year disease-free survival and overall survival from the International Duration Evaluation of Adjuvant therapy (IDEA) collaboration on 3 months versus 6 months duration of adjuvant chemotherapy in patients with stage III colon cancer. The authors should be complimented on their efforts, and the results confirm the expectations from the earlier published data on 3-year disease-free survival.2 However, the new data are important because overall survival is generally considered to be the most clinically relevant endpoint for adjuvant trials and therefore these results support the value of 3 months of adjuvant chemotherapy.

Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials

A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results. In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0-1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025. With median follow-up of 72·3 months (IQR 72·2-72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4-83·3) with 3 months of therapy and 82·8% (81·8-83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95-1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5-83·6) versus 81·2% (79·2-82·9; HR 0·96 [0·85-1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3-83·8) and 83·8% (82·6-85·0; HR 1·07 [0·97-1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02-1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded. Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration. US National Cancer Institute.

Patients' Preferences for 3 Months vs 6 Months of Adjuvant Chemotherapy for Colon Cancer.

BackgroundSCOT was an international, randomized phase 3 trial of 3 months vs 6 months of adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine in patients with colorectal cancer. We sought patients’ preferences for 3 months vs 6 months of adjuvant chemotherapy in the SCOT trial.MethodsSCOT participants from Australia and New Zealand completed a validated questionnaire (at 3 and 18 months) to elicit the minimum survival benefits judged necessary to make an extra 3 months of adjuvant chemotherapy worthwhile, based on their experience. Standardized hypothetical scenarios used the following baseline survivals (with 3 months of chemotherapy): life expectancies (LE) of 5 years and 15 years and 5-year survival rates (5YS) of 65% and 85%.ResultsOf the 160 participants, 82 were assigned 3 months adjuvant chemotherapy, and 78 were assigned 6 months. Adjuvant chemotherapy was FOLFOX in 121 (75.6%) and XELOX in 39 (24.4%). Preferences varied substantially and did not differ according to treatment group. The median survival benefits judged necessary to make the extra 3 months of chemotherapy worthwhile were an extra 3 years beyond a LE of 5 years; 3 years beyond a LE of 15 years; 15% beyond a 5YS of 65%; and 5% beyond a 5YS of 85%. Preferences were similar at 3 months and 18 months. Preferences were not predicted by participants’ baseline characteristics.ConclusionPreferences varied substantially, and the benefits many required to warrant an extra 3 months of adjuvant chemotherapy were larger than the benefits of an extra 3 months of chemotherapy calculated in the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) meta-analysis.

Impact of the IDEA Collaboration Study Results on Clinical Practice in France for Patients With Stage III Colon Cancer: A National GERCOR - PRODIGE Survey

BackgroundThe IDEA collaboration showed that the type and duration of adjuvant chemotherapy in stage III colon cancer (CC) could be adjusted according to the schedule of chemotherapy and the level of risk. We aimed at evaluating the implementation of IDEA’s results in real-life practice for stage III CC. Material and MethodsAll clinicians registered in the French oncology cooperative groups GERCOR, FFCD, and UNICANCER GI mailing lists were invited to participate to an online anonymized nationwide survey from January 30, 2019 to March 31, 2019. Proportions were compared using the χ2 test. ResultsA total of 213 physicians answered the survey. Of these, 173 (81%) considered that 3 months of adjuvant chemotherapy was the new standard of care for low-risk (pT1-3/N1) stage III CC, and 99% considered that 6 months remained the standard of care for high-risk (pT4 and/or pN2) stage III CC. In patients under 70 years, capecitabine and oxaliplatin (CAPOX) for 3 months was prescribed by 74% of the participants in low-risk CC, whereas 6 months of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was preferred for high-risk CC in 94% of cases. For patients over 70 years with good performance status and no comorbidities, 172 (81%) physicians prescribed oxaliplatin-based chemotherapy for low-risk CC (3 months, 144 of 172%; 88%), and 200 (94%) physicians prescribed oxaliplatin-based adjuvant chemotherapy for high-risk CC (6 months, 199 of 200%; 99.5%). ConclusionsThe IDEA results have been practice-changing as French physicians have implemented 3 months of CAPOX for patients with low-risk stage III CC, substituting from 6 months of FOLFOX, which remains the preferred regimen for high-risk patients.

Body mass index and body weight change during adjuvant chemotherapy in colon cancer patients: results from the AVANT trial

While obesity increases colorectal cancer incidence, there are inconsistent results in the prognostic role of obesity or body weight change on survival. This study investigated the prognostic impact of body weight and weight change in stage III or high risk stage II colon cancer patients. We used data from patients enrolled in the phase III AVANT trial. The AVANT trial investigated the efficacy of adding bevacizumab to standard adjuvant chemotherapy (FOFOX or XELOX). Weight change during the first 6 months of adjuvant chemotherapy was measured. Cox proportional hazard model was used to assess the prognostic influence of body weight and weight change. Among 3451 intention-to-treat population, body weight and weight change was measured in 3449 (99.9%) and 2455 (71.1%) patients, respectively. Among 2455 patients, 651 (26.5%) had weight gain over 5 kg and 179 (7.3%) had weight loss over 5 kg. Weight gain was more frequently observed in Asian and male. Neither baseline BMI nor weight change affected recurrence or survival in the Cox proportional hazard model.

Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial

Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point. From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority= 0.380, P for superiority= 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority= 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%. The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov, registration number: NCT0064660.

Wnt5a expression and prognosis in stage II–III colon cancer

Cancer metastases accounts for most cancer deaths. The secreting glycoprotein Wnt5a impairs tumor cell migration and reduces invasiveness and metastasis. High Wnt5a expression in tumor cells is correlated to better outcomes in patients with breast, prostate and epithelial ovarian cancer. We aimed to investigate the association between the Wnt5a expression and outcomes in patients with colon cancer (CC) stage II/III. We performed a retrospective single-center study evaluating 345 patients with radical resection for primary CC, stage II/III, who started 6 months of adjuvant chemotherapy with 5-FU or capecitabine ± oxaliplatin between 2001 and 2015. Archived formalin-fixed paraffin embedded tumor tissue from resection specimens were stained with Wnt5a antibody using immunohistochemistry. Cytoplasmatic Wnt5a staining was assessed according to intensity and percentage of stained cells. Patients were divided in groups depending on high (n = 230) or low (n = 115) Wnt5a expression. Disease free survival (DFS) and overall survival (OS) were analyzed for the two groups using Kaplan-Meier plots and Long rank test. Patients with Wnt5a-negative tumors had significantly poorer performance status (PS) than patients with high Wnt5a expression (p = 0.046). No significant difference was seen between patients with low and high Wnt5a expression in terms of 5-year DFS (p = 0.517) or 5-year OS (p = 0.415). Poor PS was associated with lower DFS (p = 0.002) and OS (p < 0.001). In conclusion, we found no significant difference in prognosis for patients with stage II/III CC depending on their Wnt5a expression. Patients with Wnt5a-negative tumors had significant poorer PS than patients with higher levels. Poor PS was associated with lower DFS and OS.

Early liver metastases after “failure” of adjuvant chemotherapy for stage III colorectal cancer: is there a role for additional adjuvant therapy?

BackgroundThe utility of adjuvant chemotherapy after resection of colorectal liver metastasis (CLM) in patients with rapid recurrence after adjuvant chemotherapy for their primary tumor is unclear. The aim of this study was to evaluate the oncologic benefit of adjuvant hepatic arterial plus systemic chemotherapy (HAIC + Sys) in patients with early CLM. MethodsA retrospective analysis of patients with early CLM (≤12 months of adjuvant chemotherapy for primary tumor) who received either HAIC + Sys, adjuvant systemic chemotherapy alone (Sys), or active surveillance (Surgery alone) following resection of CLM was performed. Recurrence and survival were compared between treatment groups using Kaplan–Meier methods and Cox proportional hazards models. ResultsOf 239 patients undergoing resection of early CLM, 79 (33.1%) received HAIC + Sys, 77 (32.2%) received Sys, and 83 (34.7%) had Surgery alone. HAIC + Sys was independently associated with reduced risk of RFS events (adjusted hazard ratio [HRadj]: 0.64, 95%CI:0.44–0.94, p = 0.022) and all-cause mortality (HRadj: 0.54, 95%CI:0.36–0.81, p = 0.003) compared to Surgery alone patients. Largest tumor >5 cm (HRadj: 2.03, 95%CI: 1.41–2.93, p < 0.001) and right-sided colon tumors (HRadj: 1.93, 95%CI: 1.29–2.89, p = 0.002) were independently associated with worse OS. ConclusionAdjuvant HAIC + Sys after resection of early CLM that occur after chemotherapy for node-positive primary is associated with improved outcomes.

Advances in the treatment of locally advanced rectal cancer

Locally advanced rectal cancer requires multidisciplinary care. In the United States, most patients are treated with neoadjuvant chemoradiation delivered over 25‐28 days, total mesorectal excision, and 4 months of adjuvant chemotherapy. While effective, this trimodal approach is arduous. Alternative approaches have emerged to streamline treatment without sacrificing oncologic outcomes. These approaches include preoperative chemotherapy with selective use of radiation, short‐course radiotherapy delivered over 5 days, and total neoadjuvant therapy with attempted nonoperative organ‐preserving management (watch and wait). Ongoing trials are assessing the efficacies of these approaches in combination with various risk stratification strategies.

Abstract 817: Pancreatic acinar carcinoma - a rare entity with a targetable BRAF V600E mutation

Abstract Background: Pancreatic acinar carcinomas account for less than 1% of all pancreatic cancers and are considered genetically distinct entities form other pancreatic carcinomas. The pathogenesis of this malignancy is incompletely understood, and the efficacy of cytotoxic chemotherapy is not well defined especially in unresectable or metastatic disease. Methods: We identified one patient with pancreatic acinar carcinoma who was treated at our institution and was found to have a unique targetable pathogenic mutation on tumor sequencing. Results: A 64-year-old male patient was diagnosed with localized pancreatic acinar carcinoma during workup for epigastric pain. He underwent distal pancreatectomy with final pathology consistent with stage T3N0 acinar cell carcinoma without any adenocarcinoma component. He subsequently received six months of adjuvant chemotherapy with gemcitabine plus capecitabine, derived from evidence on pancreatic adenocarcinoma due to the size of his original tumor. Seven months after completion of adjuvant therapy, he was found to have local recurrence within the surgical bed and was treated with three cycles of systemic chemotherapy with FOLFIRINOX. During a following planned surgical resection, multiple liver lesions were seen intraoperatively, and surgery was aborted. Liver lesions were biopsied and hybrid capture next-generation sequencing was performed which revealed: a BRAF V600E gain of function mutation, CDKN2A loss as well as MYCN amplification. The patient declined further chemotherapy and his treatment was switched to Encorafenib (BRAF inhibitor) plus Binimetinib (MEK inhibitor). He attained a partial response to therapy at his first restaging CT scan after 2 months of therapy (-39% per RECIST 1.1). Both mass at the surgical bed as well as liver metastases were decreased in size. He tolerated treatment very well without significant adverse events (including no clinically significant rash). Conclusions: While BRAF rearrangements as described in the literature may occur in 15-23% of patients with acinar cell carcinoma of the pancreas, BRAF activating mutations and in particular the BRAF V600E substitution has not been reported. This particular substitution is commonly present in melanoma, hairy cell leukemia, Langerhans cell histiocytosis and less frequently in lung and colon cancer. A combination of BRAF and MEK inhibition may be used in patients with tumors harboring this activating mutation with variable efficacy across different histologies. In light of the rarity of acinar cell carcinomas of the pancreas and the lack of established systemic treatment guidelines, tumor sequencing should be considered if no other therapies are available. This is the first case reported in the literature of a patient with acinar cancer of the pancreas and BRAF V600E mutation where targeted therapy has shown an early response. Citation Format: Vaia Florou, Chris Nevala-Plagemann, Sean Mulvihill, Ignacio Garrido-Laguna. Pancreatic acinar carcinoma - a rare entity with a targetable BRAF V600E mutation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 817.

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

Three versus six months of adjuvant chemotherapy for colorectal cancer: A multi-country cost-effectiveness and budget impact analysis.

7076 Background: The international Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority and significantly less toxicity of 3 versus 6 months of adjuvant chemotherapy for patients with colorectal cancer (CRC). This study assesses the value of shorter treatment and the economic implications of implementing the findings from the perspective of the countries that participated in the SCOT trial. Methods: Individual patient level data (n=6055) from the SCOT trial was used in a fully-pooled, cost utility analysis for the six participating countries. The incremental net monetary benefit (INMB) per patient was calculated using a willingness to pay threshold of one Gross Domestic Product per capita for each country. Responses to a clinician questionnaire (n=265 across 21 countries collected in April 2019) were used to estimate extent of practice change. The budget impact over 5 years of using shorter treatment was calculated, using 2019 and US dollars (USD) as the base year and currency, respectively. Results: Cost drivers for differences between the SCOT trial arms were reduced chemotherapy costs and fewer hospitalisations in the first treatment year. The INMB per patient of using shorter treatment and subsequent monetary impact on healthcare provider budgets resulting from implementation are shown in Table. This is a cost saving treatment strategy in all countries. The budget impact over 5 years amounts to savings of nearly half a billion USD. Conclusions: The economic burden of CRC treatment globally exceeds $39 billion per annum. Understanding the costs and consequences of widespread clinical practice change is important for optimal budget planning. This study has widened the transferability of results from a phase III cancer trial, showing shorter treatment is cost-effective from a multi-country perspective. The vast savings could provide benefit elsewhere within a limited healthcare budget, and justify the investment in conducting the SCOT trial. [Table: see text]

Long Term Survival of a Patient with Metastatic Rectal Cancer Treated with Oral Regorafenib - A Case Report

A 56-years-old female had a history of radical proctectomy for carcinoma of rectum on 2003/4/29. Pathology report was Dukes’ C adenocarcinoma with 12 of 24 lymph node showing metastasis. She was managed to have six months of adjuvant chemotherapy of 5- fluorouracil with leucovorin. Computed Tomography (CT) scan on 2013/4/16 was reported as having recurrent tumor in left presacral region with. associated left hydronephrosis and hydroureter. 5400 cGy of radiotherapy was given. CT scan on 2013/8/14 was reported as decreased size of recurrent tumor in left presacral region as compared to last CT with persistent left hydronephrosis and hydroureter due to tumor invasion of middle left ureter. She was then arranged to have chemotherapy of capecitabine, irinotecan oxaliplatin, uracil-futrafur with bevacizumab and Ziv-Aflibercept. Above knee amputation of left leg was performed on 2016/3/29 following poor result of fasciectomy for necrotizing fasciitis. CT scan on 2016/6/6 was reported as interval stable of presacral and left pelvic wall soft tissue mass with calcification, associated left hydronephrosis and hydroureter. 160 mg per day of regorafenib was started from 2016/7/14. She was taking regorafenib regularly in the past three years and 6 months with stable disease. Her last CT scan on 2019/12/27 was reported as stationary appearance of the calcified soft tissue lesion in left presacral region with ipsilateral hydronephroureter and obliteration ipsilateral common iliac vein with prominent venous collaterals in anterior wall of pelvis and with mild left thigh edematous change.

Prognostic value of circulating tumor DNA (ctDNA) detection during adjuvant chemotherapy in patients with stage III colorectal cancer: The interim report of a prospective, observational study.

29 Background: Adjuvant chemotherapy (ACT) is the standard treatment for stage III colorectal cancers (CRC). However, optimal biomarker were still needed for individualized adjuvant strategies. Here, we conducted a prospective study in patients with stage III CRCs with combined ACT, to explore the prognostic effect of circulating tumor DNA (ctDNA) before and after ACT. Methods: The study enrolled 130 patients with stage III colon and rectal cancer (≥10cm from anal) who received curative resection without neoadjuvant therapy at Fudan University Shanghai Cancer Center. All patients received 3 or 6 months of ACT. The Roche AVENIO Surveillance Kit was used to assess somatic mutations by next-generation sequencing (NGS) in tissue, pre- and post-chemo plasma samples. The plasmas were collected 3-5 weeks after surgery and after last cycle of ACT, respectively. Patients were classified as ctDNA (+) or (-) based on the detection of SNVs identified in tumor tissue at an AF of at least 5%. Results: In the interim analysis, 116 tissues, 123 pre-chemo and 98 post-chemo plasmas were prospectively collected and detected, and a total of 86 matched samples were analyzed with a median follow-up of 12.0 months. ctDNA was detectable in 14 of 86 patients (16.3%) before ACT, and in 10 (11.6%) patients after ACT. After 1-year follow-up, longitudinal ctDNA analysis identified 6 of 12 early relapses (50.0%), while 6 in 69 patients (8.7%) who were both ctDNA (-) in pre- and post-chemo samples had early relapse. Before ACT, ctDNA(+) patients were 7 times more likely to relapse early than ctDNA(-) patients (HR, 7.372; 95% CI, 1.543-35.22; P = 0.012). Similarly, after ACT, ctDNA(+) patients were 13 times (HR, 13.37; 95% CI, 2.026-88.23; P = 0.007) more likely to relapse. Monitoring after ACT indicated that 7 of the 14 ctDNA(+) patients (50.0%) were cleared, and the early relapse rate decreased from 43.9% (3/7) to 28.6% (2/7) if ctDNA turned negative. Conclusions: ctDNA analysis can potentially change the postoperative management and surveillance strategies for stage III CRC by enabling risk stratification, monitoring ACT efficacy, and detecting early relapse. Clinical trial information: ChiCTR1800018754.

Benefit of oxaliplatin in stage III colon cancer according to IDEA risk groups: Analysis of MOSAIC and C-07 trials.

118 Background: The IDEA pooled analysis compared 3 to 6 months of adjuvant chemotherapy for stage III colon cancer. The overarching goal was to reduce chemotherapy-related toxicity, mainly oxaliplatin-induced neuropathy. Patients were classified into low-risk and high-risk, suggesting low-risk patients may be offered only 3 months of treatment. In our previously published analysis using retrospective data from the National Cancer Database (NCDB) we showed similar benefit for oxaliplatin in both low and high IDEA risk groups. In the current study, we aimed to test our hypothesis using data from the two large clinical trials assessing the benefit of oxaliplatin in the adjuvant setting, namely, MOSAIC and C-07. Methods: Using the MOSAIC and C-07 previously published studies, we identified 1,754 low-risk and 1,302 high-risk individuals with stage III colon cancer, according to the IDEA classification. We used multivariate COX regression to evaluate the magnitude of survival differences between IDEA risk groups, according to oxaliplatin use. The analysis was adjusted for age, primary tumor sidedness, tumor stage, tumor grade and lymph node ratio. Results: Individuals with IDEA low-risk derived overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) benefit from the addition of oxaliplatin to adjuvant chemotherapy, with adjusted hazard ratios (HRs) of 0.78 (0.65-0.94), 0.75 (0.63-0.89) and 0.74 (0.62-0.90). Similarly, individuals with IDEA high-risk derived OS, DFS and RFS benefit from the addition of oxaliplatin to adjuvant chemotherapy, with adjusted HRs of 0.84 (0.71-0.99), 0.81 (0.69-0.95) and 0.82 (0.69-0.97). Conclusions: IDEA risk classification per se does not predict benefit from addition of oxaliplatin to adjuvant chemotherapy in stage III colon cancer, according to analysis of the MOSAIC and C-07 studies. Funding: NCI U10CA-180868, NCI U10CA-180822.

Impact of adjuvant treatment and prognostic factors in stage I uterine leiomyosarcoma patients treated in Commission on Cancer®-accredited facilities

ObjectivesDetermine the impact of adjuvant chemotherapy (ACT) and prognostic factors in surgically managed patients with stage I uterine leiomyosarcoma (ULMS). MethodsWomen who underwent hysterectomy and were diagnosed with stage I ULMS between 2010 and 2014 in the National Cancer Database were eligible for this observation study. Inverse probability of treatment weighting based on propensity score was used to balance clinical characteristics between ACT and no ACT patients. Hazard ratio (HR) and 95% confidence interval (CI) were estimated from Cox modeling. ResultsThere were 1059 eligible patients with stage I ULMS including 514 treated with ACT and 545 with no ACT. Patient characteristics and tumor features varied in patients treated with ACT vs. no ACT (P < .0001). Multivariate survival analysis demonstrated that patient age, comorbidity score, tumor size, lymphovascular space invasion (LVSI) and grade were independent prognostic factors. After propensity score weighting to control for imbalance of prognostic clinical factors, adjusted five-year survival was 61.7% vs. 61.3% and restricted mean survival time was 39.7 vs. 40.6 months for ACT vs. no ACT, respectively. Risk of death in a weighted Cox analysis of overall survival was similar (HR = 1.08, 95% CI = 0.85–1.37, P = .054) for ACT vs. no ACT patients. Subset analysis demonstrated that survival was similar in ACT vs. no ACT patients categorized by age, tumor size and LVSI or with high grade or ungraded tumors. In contrast, patients with low grade tumors had worse 5-year survival (82.3% vs. 91.5%) and an increased risk of death (HR = 3.79, 95% CI = 1.15–12.40, P = .028) following ACT vs. no ACT. ConclusionsACT did not improve survival over no ACT in patients with stage I ULMS and was inferior in patients with low grade tumors.

Survival Advantage With Adjuvant Chemotherapy for Locoregionally Advanced Rectal Cancer: A Veterans Health Administration Analysis.

Adjuvant chemotherapy (AC) after chemoradiation (CRT) and surgery for locoregionally advanced rectal cancer (LARC) is a standard of care in the United States. This study examined the role, optimal regimen, and duration of AC using data from the largest integrated health system in the United States. Using the Veterans Affairs Central Cancer Registry, patients with stage II-III rectal cancer diagnosed in 2001 through 2011 who received neoadjuvant CRT and surgery with or without AC were identified. Kaplan-Meier analysis, log-rank tests, and propensity score (PS) adjustment analysis were used to assess survival. A total of 866 patients were identified; 417 received AC and 449 did not (observation [OBS] group). Median follow-up was 109 months. Median disease-specific survival (DSS) was not reached. Six-year DSS was 73.7%; 79.5% for the AC group versus 68.0% for the OBS group. PS-matched analysis for DSS favored AC (P=.0002). Median overall survival (OS) was 90.8 months. Six-year OS was 56.7%; 64.3% for AC versus 49.6% for OBS. In PS-matched analysis, median OS was 117.4 months for AC and 74.3 months for OBS (P<.0001). A DSS advantage was seen when comparing ≥4 months with <4 months of AC (P=.023). No difference in DSS or OS was seen with single-agent versus multiagent AC. In this population of patients with LARC treated with neoadjuvant CRT and surgery, OS and DSS were improved among those treated with AC versus OBS. DSS benefits were seen with ≥4 months of AC. No additional benefit was observed with multiagent therapy. In the absence of phase III data, these findings support the use of AC for LARC.

Making sense of adjuvant chemotherapy in colorectal cancer.

Surgical resection is the only curative treatment for locoregional colon cancer. The goal of adjuvant chemotherapy is to eradicate micro-metastatic disease and improve survival. This has been most clearly demonstrated in stage III (node-positive) disease, whereas benefit of adjuvant chemotherapy in stage II disease remains controversial. In stage III colon cancer, 6 months of adjuvant chemotherapy with oxaliplatin-based chemotherapy have been accepted as the standard for the last 15 years. The recent IDEA collaboration has challenged this in 2018; while overall was a negative non-inferiority study, pre-planned subset analyses do support that for patients with low-risk stage III disease, 3 months of XELOX (capecitabine and oxaliplatin combination) is non-inferior to 6 months. In stage II colon cancer, where the potential benefit of adjuvant chemotherapy is small, the emergence of biomarkers has helped in decision-making. Tumors with deficient mismatch repair protein (dMMR) do not benefit from 5-fluorouracil-based chemotherapy. For patients with high clinicopathological risk stage II disease with proficient mismatch repair proteins and good performance status, six months of adjuvant chemotherapy is still recommended. In the management of rectal cancers, where the risk of local recurrence is higher, chemoradiation (CRT) is often included as neoadjuvant or adjuvant therapy in the management of stage II and III rectal cancer. The benefit of adjuvant chemotherapy in rectal cancer has been extrapolated from adjuvant colon cancer studies with updated results from adjuvant rectal cancer studies demonstrating similar benefits. This review summarizes the current landscape of adjuvant therapy for patients with resected stage II and III colorectal cancer.