Number Of Preoperative Cycles Research Articles

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

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

Complete pathological response after neoadjuvant treatment in soft tissue sarcoma: A single-institution experience.

e23526 Background: Pathological complete response (pCR) to preoperative treatment has been reported as a prognostic factor for survival in the soft tissue sarcoma (STS) population. pCR evaluation has been demonstrated in breast and head and neck cancers widely associated with improved outcomes, including overall survival (OS). The assessment to pathological response is not easily subject to variability, can be globally equitable, and has the potential to serve as a surrogate endpoint for research and survival outcomes. Methods: This is a retrospective, single institution study. The inclusion criteria were: patients with STS diagnosed between 2011–2021, s/p neoadjuvant treatment, and pCR (defined as necrosis rate on surgical specimen ≥ 90%). This study was approved by the University of Miami-Sylvester IRB. Results: We identified a total of 39 patients that met our inclusion criteria. 43% of the population were women. Mean age at diagnosis was 59 years old (range 20-84). 90% of the population remains alive, with mean overall survival of 6.6 years. Disease recurrence (local and distant) was present only in 11 patients (28%) and 4 of these patients (36.3%) progressed to death. Median progression free survival (PFS) was 42.5 months (95% CI 33.9-53.1). 34% of the cohort had the myxofibrosarcoma histology, and this group had mean OS of 7.2 years and mean PFS of 5.8 years. 20% of the myxofibrosarcoma patients developed metastatic disease versus 21% among patient with different histology (p = 0.89). Among the neoadjuvant treatments delivered, 93% of the patients received a combination of chemotherapy and radiation. The most common neoadjuvant chemotherapy regimen was the combination of Doxorubicin with Ifosfamide (66% of the patients) and their mean OS was 6.2 years vs 2.9 for the other regimens (p = 0.08). Among patients that received neoadjuvant chemotherapy, the median number of preoperative cycles was 4 (SD = 1.1). The median time from the start of chemotherapy to surgery was 5 months (SD = 1.4 months). Conclusions: Treatment induced pathologic necrosis has been proven as a predictor of survival in patients with STS in multiple studies. Interestingly, the most common histology present was myxofibrosarcoma, suggesting a good response to neoadjuvant treatment in this group with a lower rate of metastatic disease after pCR, when compared to the literature (35%). Chemotherapy associated with radiation in the neoadjuvant setting was the most common treatment and Doxorubicin with Ifosfamide was associated with a longer OS. The rate of necrosis after surgery has been shown to be a prognostic factor for STS, therefore there is a need to evaluate which associated factors lead to pCR. Further research with the evaluation of the molecular profiling of STS with pCR is underwork to better understand the mechanisms behind treatment responses.

Neoadjuvant chemotherapy for locally advanced colon cancer patients: Long-term results from a single institutional experience.

e15598 Background: Neoadjuvant chemotherapy (NAC) is an emerging alternative in the management of patients with locally advanced colorectal cancer (LACRC), with promising results in terms of R0 resection rates, compliance, postoperative morbidity and a trend towards reduced risk of relapse. However, more mature data are required. We evaluated the long-term outcome of this strategy in our institution. Methods: We retrospectively analysed LACRC patients treated preoperatively with either biweekly FOLFOX or XELOX at standard doses as a follow-up of our previous experience with this neoadjuvant approach. Patients were identified from a prospectively collected tumor registry database from our institution. Clinical staging was based on colonoscopy and CT-scan. Only patients with radiological signs of lymph node involvement and/or extramural invasion > 5 mm were included. The uracil/dihidrouracil ratio was calculated at baseline as a surrogate marker of DPD deficiency. Pathological tumor regression was graded according to the MSKCC and toxicity with the NCI-CTCAE 4.0. Results: From February 2006 to November 2019 91 pts with MSS LACRC (M/F: 62/29; median age 66. Clinical stage; T3: 60.4%, T4: 37.4%, N+: 75.8%; Sideness: 82.4% left located were analysed. Preoperative chemo was FOLFOX in 46 pts and CAPOX in 45 pts. Median number of preoperative cycles was 4 (range 1-10). Side effects profile included G3-4 diarrhea (3.3%), G2 sensitive neuropathy (12.1%) and G2 neutropenia (4.4%). 9 pts had a treatment delay due to haematological toxicity. No progressive disease was noted during neoadjuvant chemotherapy. All patients underwent surgery, most of them (63.7%) by a laparoscopic approach. pCR was found in 11 pts (12.1%). Grade 3, 3+ and 4 tumor regression according to MSKCC score was reached in 50.5% of the patients (Median number of harvested nodes was 17 (range 7-51), with 75.8% being ypN0. Lymphovascular and perineural invasion were found in 7.7% and 6.6% of the patients, respectively. The median hospital stay was 7 days (3-36) and 13 pts develop any surgical complication. 37.4% received adjuvant treatment. After a median follow-up of 63 months, median progression-free (PFS) and overall survival (OS) have not been reached. 5-year actuarial PFS for right and left LACRC was 77 and 87%, respectively. Conclusions: Our data add to the growing evidence suggesting that NAC may play a meaningful role in LACRC patients

Delays from neoadjuvant chemotherapy to interval debulking surgery and survival in ovarian cancer

IntroductionDelays from primary surgery to chemotherapy are associated with worse survival in ovarian cancer, however the impact of delays from neoadjuvant chemotherapy to interval debulking surgery is unknown. We sought...

Results of the IFCT 0002 phase III study comparing a preoperative and a perioperative chemotherapy (CT) with two different CT regimens in resectable non-small cell lung cancer (NSCLC)

7530 Background: Association of surgery and CT is standard for early-stage NSCLC. Meta-analyses showed comparable efficacy of adjuvant and neoadjuvant CT. The primary objective was to compare survival between two different CT strategies: all before surgery (PRE) versus perioperative (PERI). Methods: Between 2001 and 2005, 528 patients with a stage IA-II resectable NSCLC were randomized to 4 parallel arms (A: 2 GP + 2 GP in responders, then surgery, B:2 GP - surgery + 2 GP in responders, C: 2 TC + 2 TC in responders then surgery, D: 2 TC - surgery + 2 TC in responders; GP: Gemcitabine 1250 mg/m2/d1, 8 and cisplatin 75 mg/m2/d1 q3 wk; TC: Paclitaxel 200 mg/m2/d1 and carboplatin AUC 6, q3 wk). Results: 501 patients were operated on, 96.2% in the preoperative CT arms (PRE: A+C) and 95.8% in the perioperative CT arms (PERI: B+D). Ninety- day postoperative mortality was 4.9% and 4.2%, respectively. Pathological complete response was not significantly influenced by the number of preoperative cycles (PRE:8.6%, PERI:6.4%). In an intent-to-treat analysis, 3-yr survival was 67.8% and 68.6%, respectively (p=0.96). In responders, despite a dramatic difference in CT compliance (90.4% and 75.2% having received the 4 cycles, respectively, p=0.001), 3-yr survival was 75.1% and 79.5%, respectively (p=0.82). Survival did not differ with the CT regimen (GP versus TC, p=0.84). Three-yr survival increased from 68.1% in the PRE arms to 77.2% in the PERI arms in squamous cell carcinomas (SCC), and decreased from 67.7% to 61.6% in non SCC, respectively (Cox model interaction, p=0.35). Three-yr survival was 74.6% in the GP arms and 70.7% in the TC arms, in SCC, and was 64.2% and 65.4%, in non SCC, respectively (interaction, p=0.51). There was no interaction between CT strategy and stage. In stage II patients, 3-yr survival was 59.1% but 76.5% in responders, comparable to that of all stage I patients (72.9%). Conclusions: Despite an increased compliance of the all preoperative chemotherapy strategy, no difference was observed between the PRE and PERI arms. There might be an advantage for perioperative CT and for gemcitabine-based in SCC and for preoperative CT and for taxane-based in non SCC. No significant financial relationships to disclose.

Retrospective comparison of response rates and survival with neoadjuvant docetaxel versus anthracycline-based chemotherapy for locally advanced breast cancer patients

e11564 Background: LABC is a major problem in our country comprising of ≥ 20% of all breast cancer patients. Neoadjuvant chemotherapy is now standard treatment for LABC but randomized trials have failed to show survival advantage. Methods: We retrospectively analyzed locally advanced breast cancer (stage III) patients who received neoadjuvant chemotherapy (NACT) from January 2000 to December 2008. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment-naïve patients started on NACT were analyzed. Ninety one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological CR (pCR) was defined as no evidence of malignancy in both breast and axilla. Survival curves generated using Kaplan-Meier method and survivals compared using log-rank test. Results: Median age of whole cohort was 45 years (range 25–68 years). Premenopausal were 42% and ER+ 49.5%. Most (90%) were T4 tumors and 70% were stage IIIB. Median number of preoperative cycles was 3 and 6 in D and A group. Overall clinical response rates for breast primary were 74.3% (CR 28.6%) and 53.7% (CR 16.7%, p=0.58) while for axilla ORR were 75.7% (51.4% CR) vs 54.8% (40.4% CR, p=0.77) respectively for D and A. Corresponding pCR rates were 19% vs 13% respectively. There was no significant difference in disease free (3 year 56.84% vs 61.16%, p=0.80) and overall survival (3 year 70% vs 78.5%, p=0.86) between two groups. Those who achieved pCR in both groups also had no survival advantage (p=0.34) over non achievers. There was no difference in pCR rates for ER+ vs ER- patients but ER+ patients had significantly higher DFS than ER- patients (p=0.05). Conclusions: Although pCR rates were higher with docetaxel based NACT, it did not translate into superior DFS/OS compared to anthracycline based chemotherapies. Achievement of pCR too, was not associated with any survival advantage. No significant financial relationships to disclose.

IFCT0002 phase III study comparing a preoperative (PRE) and a perioperative (PERI) chemotherapy with two different CT regimens in resectable non-small cell lung cancer (NSCLC): Early results

7519 Background: Recent trials have shown a survival benefit of CT in resectable NSCLC. The primary objective was to define the best timing of CT (all before surgery versus perioperative). Another objective was to compare two regimens, gemcitabine-cisplatin (GP) and paclitaxel-carboplatin (TC). Methods: Between May 2001 and Dec 2005, 528 patients (pts) with a stage IA-II resectable NSCLC were randomized to 4 parallel arms: A: 2 GP + 2 GP in responders, then surgery, B: 2 GP - surgery + 2 GP in responders, C: 2 TC + 2 TC in responders then surgery, D: 2 TC - surgery + 2 TC in responders (GP: Gemcitabine 1250 mg/m2/d1, 8 and cisplatin 75 mg/m2/d1 q3 wk; TC: Paclitaxel 200 mg/m2/d1 and carboplatin AUC 6, q3 wk). Results: Pathological tumor volume and pathological complete response rate did not differ with the number of preoperative cycles. Proportions of pts receiving cycles 3 and 4 were higher when all CT was given before surgery. There were several significant differences in the main toxicities between GP and TC. Conclusions: 1- GP and TC were effective and safe. 2- Results of pathological response suggested that 2 cycles might be as effective as 4 cycles. 3- Dose intensity was higher when all chemotherapy was given before surgery compared to both before and after surgery. No significant financial relationships to disclose. [Table: see text]

Effectiveness of neoadjuvant chemotherapy including bevacizumab in patients with resectable colorectal cancer liver metastases

4060 Background: Chemotherapy including bevacizumab has become the new standard in the first line treatment of patients with metastatic colorectal cancer (mCRC). Response to chemotherapy has been assessed as major prognostic factor for RFS in resectable mCRC patients, but safety concerns have been raised. We conducted a phase II trial to evaluate the safety of neoadjuvant chemotherapy including bevacizumab (Bev). Methods: Patients with resectable mCRC received six cycles (3 months) of neoadjuvant XELOX (capecitabine 3,500mg/m2/day days 1–7 plus oxaliplatin 85mg/m2 day 1) with bevacizumab (5mg/kg) every 2 weeks. The sixth cycle did not include Bev resulting in a gap of 5 weeks between last Bev and surgery. Primary end points were feasibility of neoadjuvant treatment with this regimen and response rate; secondary end points were feasibility of curative liver resection and perioperative morbidity of the surgical procedure. Results: 54 patients (32 male, 22 female) with a median age of 61 years (SD ± 10.6) were included. The median number of preoperative cycles was 6 (SD ± 2). Grade 3/4 side effects were PNP in 13%, H&F in 3%, diarrhea in 38%, anaemia in 3% and neutropenia in 12% of our patients. Thromboembolic events occurred in 4 patients (7%), hypertension grade III in 2 (4%) and perforation in 1 (2%) patients. A dose reduction of chemotherapy was required in 43%. There were no treatment related deaths. The overall objective response rate for all 54 patients was 74% (40 patients) including 11% pCR. 11 additional patients (20%) had stable disease and only 3 (6%) progressed. Potential curative surgery was performed in all but 5 patients (91%). 2 patients were not resected due to PD, 2 because of pulmonary embolism during chemotherapy and 1 patient because of positive hilar lymph nodes. Conclusions: These data provide evidence that neoadjuvant chemotherapy including bevacizumab can be safely administered in patients with resectable mCRC. A high response rate and a disease control rate of 94% suggest that XELOX + Bev is an effective regimen in this treatment setting. No significant financial relationships to disclose.