Toxicity Of Neoadjuvant Chemotherapy Research Articles

Efficacy of neoadjuvant CapeOX/mFOLFOX6 without radiation for patients with baseline resectable mid-low locally advanced rectal cancer.

Chemotherapy without radiationtherapy for locally advanced rectal cancer (LARC) has attracted increasing attention, but the optimal schema remains controversial. In this study, we aimedtoassess the efficacy and toxicity of neoadjuvant chemotherapy (nCT) of two regimens for patients with mid-low baseline resectable LARC. A retrospective study was performed in 131 patients withbaseline resectable LARC in a single center between April 2016 and August 2020. All patients received four cycles of neoadjuvant CapeOX or mFOLFOX6beforesurgery. Clinical characteristics, pathological response, and survival status were then assessed. After a 1:1 propensity score matching, 96 patients were enrolled, including 48 receiving CapeOX and 48 receiving mFOLFOX6. The objective regression rates were 50.00% and 58.33%, and the pathological complete response rates were 6.25% and 8.33%, respectively,intheCapeOXandmFOLFOX6groups. Patients who received mFOLFOX6 had a better tumor regression grade (TRG) than those who received CapeOX (P=0.005). Patients in both groups had similar survival outcomes. ThenCT has shown promising tumor response and survival outcomes, which can be atreatment optionfor baseline resectable LARC. For the two regimens, mFOLFOX6 provided better TRG than CapeOX, although no differences were observed in disease-free survival and OS.

Comparison of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiotherapy vs. Concurrent Chemoradiotherapy Alone in Locally Advanced Cervical Cancer Under 2018FIGO Staging Correction

<h3>Purpose/Objective(s)</h3> According to NCCN guidelines, concurrent chemoradiation (CCRT) is the standard care for locally advanced cervical cancer (LACC) patients, but the benefit of neoadjuvant chemotherapy (NACT) before CCRT for LACC patients is still controversial, especially based on 2018FIGO staging,This study is designed to answer the question by comparing the efficacy and toxicities of neoadjuvant chemotherapy with concurrent chemoradiation (NACT+CCRT) versus concurrent chemoradiation (CCRT) alone in LACC under 2018FIGO staging correction. <h3>Materials/Methods</h3> Patients with stage IB2, IIA2, IIB-IVA (2009 FIGO staging) cervical cancer were retrospectively reviewed from January 2013 to January 2017 in China. All patients were re-staged after 2018FIGO staging correction. All patients were treated with IMRT to 50.4 Gy with concurrent weekly cisplatin 40 mg/m² followed by intra-cavitary brachytherapy. The primary endpoint was progression free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response by RECIST 1.1 criteria, and toxicities. Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated with Log-rank test. Toxicities were analyzed using the χ2 test. All statistical tests were two-sided. <h3>Results</h3> A total of 432 patients were identified and 406 were eligible for analysis. The 2009FIGO staging of IB2 in 81, stage IA2 and IIB in 119, stage III in 119, stage IV in 87 were corrected into 2018FIGO staging which IB3 in 58, stage IIA2 and IIB in 75, stage III in 186, and stage IV in 87. No patients were down-staged. 201 patients were treated with NACT+CCRT and 205 with CCRT. With a median follow-up of 58.6 months, 5-year PFS was 60.3% in the NACT+CCRT arm, and was 57.6% in the CCRT arm. There was no significant difference in 5-year PFS between two arms (p=0.287). 5-year OS was 68.8% and 65.0% in the NACT+CCRT arm and CCRT+ACT arm, respectively. There was no statistical difference in 5-year OS between two arms (p=0.301). Multivariate analysis showed that pathological type, FIGO stage and pelvic nodes status were associated with OS and PFS. The CR and PR in NACT group was similar to the CCRT group (196/201 versus 193/205, p=0.090). There were higher acute systemic side effects in the NACT+CCRT arm. The result of subgroup analysis showed that PFS in stage III in NACT+CCRT group was significantly higher than that in CCRT group (57.6% vs 45.4%, P=0.048), but OS had no significant difference (71.9% vs 56.3%, P=0.053). In stage III, the curative effect of IIIC1 was better than that of IIIA-B and IIIC2, with 5-year OS of 81.9%, 61.7% and 37.5% (P=0.004), and 5-year PFS of 62.6%, 48.8% and 38.4% (P=0.031), respectively. <h3>Conclusion</h3> For LACC patients with 2018 FIGO correction stage, neoadjuvant chemotherapy plus concurrent cisplatin chemoradiation did not improves RR, PFS and OS. There were more toxicities for the neoadjuvant chemotherapy group. Further research and longer follow up is needed, especially for the staging IIIC1 LACC patients.

TREATMENT OUTCOME AND TOXICITY OF NEOADJUVANT CHEMOTHERAPY FOLLOWED BY CONCOMITANT CHEMORADIOTHERAPY VERSUS CONCOMITANT CHEMORADIATION ALONE IN LOCALLY ADVANCED CERVICAL CARCINOMA: A COMPARATIVE STUDY

Objectives: This study intended to explore the outcome, and toxicities of neoadjuvant chemotherapy in addition to standard treatment concomitant chemoradiation in locally advanced cervix cancer. Methods: Sixty-two (n=62) locally advanced cervical carcinoma patients were randomized into two arms: The controlled arm (30 patients) received concomitant chemoradiation with external beam radiation therapy of 50 Gy to the whole pelvis and Inj. Cisplatin (40 mg/m2/week) alone and the study arm (32 patients) received three cycles, neoadjuvant chemotherapy with Inj. Paclitaxel (175 mg/m2), and Inj. Cisplatin (75 mg/m2) at 3 weekly intervals, followed by concomitant chemoradiation with external beam radiation therapy (EBRT) of 50 Gy to whole pelvis and Inj. Cisplatin (40 mg/m2/week). Responses to treatment, toxicities, disease-free survival, and progression-free survival (PFS) were analyzed in both arms. Results: Among the total of 62 patients, 30 were in the concomitant chemoradiation alone arm and 32 were in neoadjuvant chemotherapy followed by the concomitant chemoradiation arm. The median follow-up period was about 13 months. The tumor response in the form of complete or partial responses was equivalent in the two arms. The disease-free survival and the PFS were also comparable in both arms. The acute and the late toxicities were also comparable in the two arms. Conclusions: This study showed that neoadjuvant chemotherapy with paclitaxel and cisplatin before definitive concomitant cisplatin-based chemoradiation can be used as an alternative in the management of locally advanced carcinoma of the cervix.

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases

BackgroundThe optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases.MethodsAdult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated.ResultsA total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3–4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively.ConclusionsNeoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Neoadjuvant chemotherapy followed by radical surgery in locally advanced vulvar carcinoma: a single-institution experience.

Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. Fourteen patients (93%) completed NACT with tolerable toxicities (G3-G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.

Prognostic Nutritional Index (PNI) in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy as a Useful Prognostic Indicator.

ObjectivePrognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).MethodsA total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (<51) and a high PNI group (≥51). The associations between breast cancer and clinicopathological variables by PNI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC).ResultsThe results indicated that PNI had prognostic significance by an optimal cutoff value of 51 on DFS and OS in univariate and multivariate Cox regression survival analyses. Breast cancer patients with a high PNI value had longer DFS and OS than those with a low PNI value [47.64 vs. 36.60 months, P < 0.0001, hazard ratio (HR) = 0.264, 95%CI = 0.160–0.435; 73.61 vs. 64.97 months, P < 0.0001, HR = 0.319, 95%CI = 0.207–0.491, respectively]. Furthermore, the results indicated that patients with high PNI had longer DFS and OS than those with low PNI in early stage and advanced breast cancer, especially in advanced breast cancer. The mean DFS and OS times for breast cancer patients with high PNI by the log-rank test were longer than in those with low PNI in different molecular subtypes. Moreover, the mean DFS and OS times in patients with high PNI by the log-rank test were longer than in those patients with low PNI without or with lymph vessel invasion. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the PNI had no significance on the toxicities of all enrolled patients, except in anemia, leukopenia, and myelosuppression.ConclusionPretreatment PNI with the advantages of being convenient, noninvasive, and reproducible was a useful prognostic indicator for breast cancer patients receiving neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Upgraded nomograms for the prediction of complications and survival in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by hepatic resection.

BackgroundTo establish upgraded nomograms incorporating neoadjuvant chemotherapy (NAC)-related factors and preoperative testing markers to predict postoperative complications, progression-free survival (PFS) and overall survival (OS) in patients with colorectal liver metastases (CRLM).MethodsMultivariate regression analyses were used to reveal independent predictors for postoperative complications, PFS and OS. Nomograms incorporating independent predictors were constructed, and discrimination and calibration were evaluated. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test.ResultsA nomogram predicting postoperative complications was constructed based on preoperative serum gamma-glutamyl transpeptidase (GGT) ≥36 U/L, major liver resection, intraoperative blood loss ≥300 mL, primary site located in the right hemicolon and primary lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.750. The calibration curves and Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 4.47, P=0.88). Moreover, a nomogram for the prediction of PFS was constructed based on tumour regression grade (TRG), primary lymph node metastasis, R0 resection and NAC cycles ≥5, with good discrimination (C-index: 0.663±0.024) and calibration, and one for predicting OS was constructed based on preoperative GGT ≥36 U/L, NAC toxicity, NAC cycles ≥5, primary lymph node metastasis and R0 resection, with favourable discrimination (C-index: 0.684±0.030) and calibration. Significant differences in PFS and OS were observed among patients stratified into three different risk groups (P<0.001) according to total scores based on the nomograms.ConclusionsThis study is the first to establish novel predictive nomograms specifically incorporating TRG, NAC toxicity and serum GGT level for the prediction of postoperative complications, PFS and OS in CRLM patients. The nomograms exhibit favourable discrimination and calibration to guide personalized CRLM management and therapy.

Pretreatment Systemic Inflammation Response Index in Patients with Breast Cancer Treated with Neoadjuvant Chemotherapy as a Useful Prognostic Indicator.

Background and ObjectiveSystemic inflammation response index (SIRI=N×M/L), based on neutrophil (N), monocyte (M), and lymphocyte (L) counts, is used to predict the survival of patients with malignant tumors and can fully evaluate the balance between host immune and inflammatory condition. The present study is aimed to evaluate the potential prognostic significance of SIRI in patients with breast cancer undergoing neoadjuvant chemotherapy.Subjects and MethodsA total of 262 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of SIRI by receiver operating characteristic curve stratified patients into low SIRI (<0.85×109/L) group and high SIRI (≥0.85×109/L) group. The associations between breast cancer and clinicopathological variables by SIRI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SIRI. The toxicity of neoadjuvant chemotherapy was evaluated by the National Cancer Institute Common Toxicity Criteria (NCICTC).ResultsThe results were shown that SIRI had prognostic significance by optimal cutoff value of 0.85×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Compared with patients who had high SIRI, patients with low SIRI had longer DFS and OS (41.27 vs 30.45 months, HR: 1.694, 95% CI: 1.128–2.543, P=0.011; 52.86 vs 45.75 months, HR: 1.288, 95% CI: 0.781–3.124, P=0.002, respectively). The patients with low SIRI had better 3-, 5-, and 10-year rates of DFS and OS than those with high SIRI. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the SIRI had no significance on toxicities of all enrolled patients, excepted diarrhea. In patients without neural invasion, those with low SIRI had better prognosis and lower recurrence rates than those with high SIRI.ConclusionPretreatment SIRI with the advantage of repeatable, convenient, and non-invasive is a useful prognostic indicator for breast cancer patients who received neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Pre-treatment systemic immune-inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy.

The systemic immune‐inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut‐off value of SII was divided into two groups: low SII group (<602 × 109/L) and high SII group (≥602 × 109/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi‐squared test or Fisher's exact test. The Kaplan‐Meier plots and log‐rank test were used to determine clinical outcomes of disease‐free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718‐1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707‐1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3‐, 5‐ and 10‐year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre‐treatment SII with the advantage of reproducible, convenient and non‐invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Comparative Toxicities of Neoadjuvant Chemotherapy With or Without Bevacizumab in HER2-Negative Breast Cancer Patients: A Meta-analysis.

Background: The addition of bevacizumab to neoadjuvant chemotherapy improves the pathological complete response rate of human epidermal growth factor 2 (HER2)-negative breast cancer patients. However, the characteristics of adverse events associated with the use of bevacizumab should receive more attention from clinicians. Objective: This meta-analysis aimed to detect the adverse events of adding bevacizumab to neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in HER2-negative breast cancer patients. Methods: PubMed, Cochrane Library, Web of Science, and EMBASE databases were systematically accessed to find eligible studies from January 1, 2000, to October 20, 2019. Reference lists were searched for additional studies. Pooled risk ratios for adverse events of bevacizumab were meta-analyzed. Results: Overall, 6 of 829 initially identified studies met the inclusion criteria, with 4681 patients randomized (2321 in the bevacizumab plus neoadjuvant chemotherapy group and 2360 in the neoadjuvant chemotherapy group). The incidence of grade ≥3 hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia significantly increased in patients treated with bevacizumab plus neoadjuvant chemotherapy. However, adding bevacizumab to neoadjuvant chemotherapy was not associated with increasing the incidences of grade ≥3 proteinuria, dyspnea, heart failure, peripheral neurotoxicity, thrombosis, thrombocytopenia, fatigue, leucopenia, vomiting, nausea, and diarrhea. Conclusion and Relevance: Adding bevacizumab to neoadjuvant chemotherapy to treat HER2-negative breast cancer patients increased adverse events. However, most adverse events are clinically manageable. Patients, therefore, need to be monitored carefully for hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia when treated with bevacizumab and neoadjuvant chemotherapy simultaneously.

Effects of Neoadjuvant Chemotherapy Toxicity and Postoperative Complications on Short-term and Long-term Outcomes After Curative Resection of Gastric Cancer

BackgroundWhether neoadjuvant chemotherapy (NAC) increased the risk of postoperative morbidities for patients with locally advanced gastric cancer (GC) is unknown. Whether neoadjuvant chemotherapy toxicity (NCT) and postoperative complications (POCs) correlate with short-term and long-term outcomes also remains unclear. We aimed to evaluate the role of NAC on the development of POCs, as well as the impact of NCT and POCs on postoperative and oncologic outcomes in curatively resected GC treated with NAC. MethodsThis study retrospectively reviewed 230 patients who underwent curative gastrectomy for locally advanced GC (clinically T3/4 or N+) after NAC between 2006 and 2016. Five hundred patients undergoing upfront and curative surgery were selected as a control group. After matching, the incidence of POCs was compared between two groups. In the NAC group, clinicopathological characteristics of patients who experienced POCs were compared to those who did not. Logistic and Cox multivariate regression analyses were used to examine factors associated with POCs, disease-free survival (DFS), and overall survival (OS). ResultsFollowing matching, 230 and 230 patients treated with surgery plus NAC and upfront surgery remained, respectively. The incidence of POCs was 28.7% and 24.3%, respectively (p = 0.290). In the NAC group, NCT (OR [odds ratio] 22.968, 95% CI [confidence interval] 2.948–> 99, p = 0.003) and operation time (OR 1.006, 95% CI 1.001–1.011, p = 0.021) were independent predictive factors of POCs. NCT did not affect oncologic outcomes. The Cox regression model demonstrated that POCs were independently associated with worse DFS (HR [hazard ratio] 2.128, 95% CI 1.240–3.653, p = 0.006) but not OS for patients treated with NAC. ConclusionsThe administration of NAC is not associated with an elevated risk of POCs. For patients treated with NAC, NCT is an independent predictor of POCs, but does not affect oncologic outcomes. POCs is independently associated with worse DFS but not OS. NAC should be considered a safe approach in patients who have locally advanced GC. Strategies to minimize chemotherapy toxicity and postoperative morbidities associated with NAC are warranted.

Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer and Its Impact on Surgical Morbidity and Oncological Outcomes: A Real-World Experience

Objectives: The purpose of this study was to investigate the impact of neoadjuvant chemotherapy (NAC) on perioperative morbidity and on oncological outcomes according to the type of chemotherapy regimen administered to patients with muscle-invasive bladder cancer (MIBC) who subsequently underwent radical cystectomy (RC).Methods: Data were collected retrospectively on 40 patients with bladder urothelial carcinoma who had at least two cycles of NAC, followed by RC, from 2011 to 2015 at our institution. The outcomes evaluated were NAC toxicity, perioperative complications, cancer-specific, and overall survival.Results: Among these cases, 23 patients (57.5%) received methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), 4 patients (10%) received gemcitabine and cisplatin (GC), and 13 patients (32.5%) received other regimes. The early and late postoperative complication rates were 35% and 12.5%. Regarding toxicity, 85% of patients had at least one side effect of NAC, but only 21.7% discontinued therapy in the MVAC group. The pathological complete response (pCR) rates for cisplatin-based regimens (MVAC and GC) and other regimens were 44.4 and 15.4%, respectively, (p = 0.09). The pathological partial response (pPR) rates for cisplatin-based regimens and other regimens were 66.7 and 15.4%, respectively, (p = 0.002). Patients treated with a cisplatin-based chemotherapy regimen had longer overall survival than those treated with other regimen (median 38.1 vs. 18.4 months, p = 0.01).Conclusions: NAC administration was not associated with high toxicity or surgical morbidity. The pathological response rates and survival outcomes in the cisplatin-based regimens were higher than with those with non-cisplatin-based regimens. These data support the use, in patients elective to a neoadjuvant setting prior to RC for MBIC, of a cisplatin-based regimen.

Overall survival in patients with residual disease after radical cystectomy and neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with urothelial carcinoma (UC). However, there are a subset of patients who do not respond or progress despite systemic treatment. Data from the National Cancer Database on patients who underwent a radical cystectomy (RC) with or without NAC from 2006 to 2013 were abstracted. Covariates were balanced using inverse probability weighting methods. The primary outcome of overall survival in patients with residual disease by stage was evaluated using 90-day conditional landmark analysis and Cox proportional hazards modeling. Secondary outcome of predictors of residual disease was evaluated using multivariable logistic regression analysis. A total of 20,128 patients met our inclusion criteria; 16,058 patients underwent RC only (80%) and 4070 underwent RC with NAC (20%). Patients who received NAC were younger and healthier, treated at an academic center, and presented with higher stage. NAC was associated with improved overall survival amongst patients with cT3-4aN0 (HR 0.84 95% CI 0.73-0.97; p = 0.02) and cN+ (HR 0.70, 95% CI 0.58-0.86; p = 0.001). Predictors of no residual disease were NAC (OR 0.17, 95% CI 0.14-0.21; p < 0.001) and treatment at an academic facility (OR 0.47, 95% CI 0.37-0.60; p < 0.001). Patients with cT3-4a or cN+ had increased odds of having residual UC (OR 2.01, 95% CI 1.53-2.64; p < 0.001, and OR 2.14, 95% CI 1.43-3.21; p < 0.001, respectively) compared with cT2. In patients with residual UC, NAC is associated with a significant survival benefit in higher stage disease only. Furthermore, those treated with NAC or at an academic center were less likely to have residual disease. Given the toxicity of NAC, more prudent patient selection for NAC is warranted and requires further study.

A phase III, multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stage IIA-IIIB esophageal squamous cell carcinoma.

The survival benefits of neoadjuvant chemotherapy (NAC) for esophagus squamous cell carcinoma (ESCC) remains controversial. The surgical procedure was not well defined in NAC strategy, in past trials. The different surgical procedure and different levels of lymphadenectomy may decrease the survival benefits from NAC. The new chemotherapy regimen with paclitaxel is promising. The purpose of this study is to confirm the superiority of paclitaxel, cisplatin and McKeown esophagectomy with total two-field lymphadenectomy compared with surgery alone for ESCC. A two-arm phase III trial was launched in June 2015. A total of 528 patients will be recruited from eight Chinese institutions within 2.5 years. The overall survival (OS) is the primary endpoint, and the secondary endpoints include disease-free survival (DFS), R0 resection rate, complication rate, perioperation mortality, days of hospitalization, quality of life (QOL), NAC response rate, pathologic response rate, toxicities of NAC, prognostic factors, predictive factors, progression-free survival (PFS), and adverse events. The study will provide the final conclusion of NAC for ESCC in China. NCT02442440 (https://register.clinicaltrials.gov/).

A comparative evaluation of neoadjuvant chemotherapy followed by concomitant chemoradiation versus accelerated radiation therapy versus conventional radiation therapy in a locally advanced head and neck carcinoma

Abstract Context: Head and neck cancers (HNCs) include malignancies of oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses, and major and minor salivary glands. Worldwide incidence of HNC cases is 4.8%, whereas in India, it is 14.3%. Aims: Evaluation and comparison of the efficacy, tolerability, and toxicity of neoadjuvant chemotherapy (NACT) with docetaxel, carboplatin, and 5-fluorouracil (TPF) followed by concomitant chemoradiation in one group, accelerated radiation therapy (RT) in second group, and conventional RT in third group. Subjects and Methods: The present randomized prospective study was conducted on locally advanced head and neck carcinoma patients who were randomly divided into three groups. All patients received NACT with 3-weekly TPF, for 3-courses. Group I-patients received concomitant conventional RT, 64 Gy/32 fractions/6.2-week along with three weekly carboplatin 300 mg/m2 × 3-cycles. Group II-patients received accelerated RT given six fractions per week, total dose 64 Gy/32 fractions/5.2-week. Group III-patients received conventional RT, 64 Gy/32 fractions/6.2-week. Results: The overall response rate to NACT was 100% in all groups. At last follow-up, in Group I – 52% remained alive with no evidence of disease (NED), 39% remained alive with residual disease, and 9% had locoregional recurrence. In Group II – 46% remained alive with NED, 46% remained alive with disease, 8% had locoregional recurrence, whereas in Group III – 40% remained alive with NED, 44% remained alive with disease, and 16% had locoregional recurrence. Conclusions: NACT followed by concomitant chemoradiation is a better treatment protocol as compared to accelerated RT or conventional radiotherapy, in terms of better complete response rates with acceptable toxicity profile.

B35 - Neo-adjuvant treatment in patients with pancreatic cancer with nab-paclitaxel and gemcitabine

Purpose: Pancreatic adenocarcinoma remains one of the deadliest forms of cancer. In this study, we analyzed the efficacy, and toxicity of neo-adjuvant chemotherapy in the treatment of for borderline resectable or unresectable locally advanced pancreatic cancer. Methods: Fifteen patients affected by locally advanced pancreatic cancer treated with nab-paclitaxel and gemcitabine chemotherapy were evaluate. Median age was 55 years (range 47-69 years). The most frequently ECOG performance status were 1 (65%). The majority of the patients has a borderline resectable disease. (65%). Acute toxicity was prospectively recorded weekly using RTOG and NCI common toxicity criteria.(65%). Results: Within a median follow-up of 16.5 months (range 4-21 months), the majority of the patients received 6-7 of the 9 scheduled cycles of nab-paclitaxel and gemcitabine:: dose reduction were necessary in the 70% of patients. One of patients (15%) achieved a complete response: this patient received also radiotherapy. Partial response were achieved in 15% of patients and stable disease in 75%. Conclusions: Despite the brief period of follow-up and the small number of patients, we conclude that nab-paclitaxel and gemcitabine chemotherapy (+/- radiotherapy) is a valid option in locally advanced pancreatic cancer.

Trends in the use and impact of neoadjuvant chemotherapy on perioperative outcomes for resected gastric cancer: Evidence from the American College of Surgeons National Cancer Database

Standard of care for patients with advanced gastric cancer includes administration of neoadjuvant chemotherapy (NAC) before resection. This study assesses the pattern of use and impact of NAC on perioperative outcomes in US medical centers. Using the American College of Surgeons National Cancer Database, 16,128 patients underwent gastrectomy for cancer from 2003 to 2012. Treatment groups were categorized as NAC or no NAC (ie, adjuvant chemotherapy and surgery only). Univariate and multivariate analyses were performed to estimate trends in utilization and impact of treatment on perioperative outcomes. Of patients undergoing gastrectomy, 36.6% received NAC and 63.4% did not receive chemotherapy in the neoadjuvant setting. Patients who received NAC were more frequently younger, male, white, privately insured, with fewer comorbidities, and treated at an academic center (all P < .0001). After controlling for demographics, comorbidities, and tumor-related factors, patients who received NAC had a postoperative duration of stay 0.43 days shorter than patients who did not receive chemotherapy (5.79 vs 6.22 days; P = .050). They had a 36% lower odds of 30-day mortality (odds ratio, 0.64, P < .0001) but nonsignificant lower odds of 90-day mortality. Use of NAC increased annually, with the greatest increases seen in academic facilities and in the Northeast and North Central United States. With concerns regarding the toxicity of NAC, these findings suggest that NAC is not associated with worse postoperative outcomes. In light of evidence touting the benefits of NAC, its adoption as a component in the multimodality care of gastric cancer is slowly increasing, although use of NAC remains poor overall.

A Phase II Trial of Neoadjuvant Chemotherapy with Genexol® (Paclitaxel) and Epirubicin for Locally Advanced Breast Cancer.

PurposeNeoadjuvant chemotherapy (NC) is yet to be established as the definitive treatment regimen for locally advanced breast cancer (LABC). The aim of this study was to determine the efficacy and toxicity of NC with epirubicin and paclitaxel.MethodsBetween March 2007 and January 2009, 50 patients with LABC were enrolled in an open-label, phase II, multicenter study carried out at five distinct institutions. All patients were scheduled to receive four cycles of 60 mg/m2 epirubicin and 175 mg/m2 paclitaxel every 3 weeks, preoperatively, unless they developed profound side effects or disease progression. After curative surgery, two additional cycles of chemotherapy were administered to patients who had shown a positive response to NC.ResultsIn all, 196 cycles of chemotherapy were administered preoperatively; 47 of the 50 patients (94%) underwent all four cycles of designated treatment. Complete disappearance of invasive foci of the primary tumor, and negative axillary lymph nodes were confirmed in eight patients (16.0%), post operation. The cumulative 5-year disease-free survival rate was 70.0% for patients with complete remission (CR) and partial remission (PR), and 33.3% for patients with stable disease (SD) and progressive disease (PD) (p=0.018). The cumulative 5-year overall survival was 90.0% for patients who achieved CR and PR and 55.6% for patients who had SD and PD (p=0.001). Neutropenia (42.0%) was the most common grade 3/4 toxicity. However, none of the toxicities resulted in cessation of the treatment.ConclusionThe encouraging pathologic response observed in the patients treated with epirubicin plus paclitaxel NC in this study suggests that epirubicin could be a substitute for doxorubicin, which is the most cardiotoxic agent.

Acute toxicity of neoadjuvant chemotherapy in oral cavity cancers: Can it be predicted?

e17027 Background: Neoadjuvant chemotherapy administration is associated with significant amount of morbidity and around 2-3% mortality in the Western world protocol settings. In developing countries where malnourishment is prevalent, the same data might not apply. Methods: This analysis was performed on a database of patients undergoing NACT for oral cancers at our center from 2010- 2012. The toxicity was graded according to CTCAE version 4.02 scale. Descriptive analysis, univariate and multivariate analysis were performed to determine factors affecting toxicity. Results: There were 528 patients, the median age was 45 years (22-78 years). The regimens administered were TPF in 35 patients (6.6%) and taxane with platinum in the rest. At least one cycle of chemotherapy was taken at our center by 94.8% (494). The median number of cycles were 2. The any grade toxicity after 1st cycle of chemotherapy were vomiting, diarrhea, mucositis, fatigue, febrile neutropenia (FN), peripheral neuropathy, hyponatremia, hypokalemia, hperkalemia, transaminitis were in 41.3% (204), 43.9% (217), 44.3% (219), 47.2% (233), 7.2% (35), 3.0% (15), 33.8% (167), 14.4% (71), 4.9% (24) and 12.3% (61).Toxicity details of second cycle of chemotherapy were available for 390 patients. The any grade toxicity after 2nd cycle of chemotherapy were vomiting, diarrhea, mucositis, fatigue, febrile neutropenia, peripheral neuropathy, hyponatremia, hypokalemia, hyperkalemia, transaminitis were in 28.6% (113), 37.3% (108), 31.3% (124), 39.3% (116), 3.1 % (12), 3.2% (13), 19.7 % (74), 7.4% (30), 3.1% (12) and 4.9% (19). For diarrhoea, female sex, nutrition (BMI below 18.5 KG/m2) and use of 3 drug regimen were predictive. For development of mucositis only nutrition was predictive. Use of 3 drug regimen and overnourishment were predictive of FN. Use of 3 drug regimen and use of docetaxel were predictive for hyponatremia. On multivariate analysis for diarrhoea only nutrition was predictive (p=0.017), for FN both drug regimen (p=0.003) and over nutrition (p=0.035) were predictive and for hyponatremia only use of 3 drug regimen was significant (p=0.017). Conclusions: 3 drug regimen, malnourishment and use of docetaxel are important predictors of acute toxicity associated with NACT in oral cancers.

D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

BackgroundPatients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT) following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature.MethodsAnalysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperative outcomes and histopathological responses to NACT were analyzed. The data is presented and compared to a cohort of patients undergoing upfront surgery in the same time period.ResultsIn this study, 139 patients (42 female and 97 male patients, median age 53 years) with gastric adenocarcinoma received NACT. Chemotherapy-related toxicity was noted in 32% of patients. Of the 139 patients, 129 underwent gastrectomy with D2 lymphadenectomy, with 12% morbidity and no mortality. Major pathological response of primary tumor was noted in 22 patients (17%). Of these 22 patients, lymph node metastases were noted in 12 patients. The median blood loss and lymph node yield was not significantly different to the 62 patients who underwent upfront surgery. Patients who underwent upfront surgery were older (58 vs. 52 years, P <0.02), had a higher number of distal cancers (63% vs. 82%, P <0.015) and a longer hospital stay (11 vs. 9 days, P <0.001).ConclusionsPerioperative outcomes of gastrectomy with D2 lymphadenectomy for locally advanced, resectable gastric cancer were not influenced by NACT. The number of lymph nodes harvested was unaltered by NACT but, more pertinently, metastases to lymph nodes were noted even in patients with a major pathological response of the primary tumor. D2 lymphadenectomy should be performed in all patients irrespective of the degree of response to NACT.