Retrospective review of total neoadjuvant therapy

BACKGROUND Neoadjuvant chemoradiotherapy(nCRT)followed by resection and postoperative multi-agent chemotherapy(maChT)is the standard of care for locally advanced rectal cancer.Using this approach,maChT administration can be delayed for several months,leading to concern for distant metastases.To counteract this,a novel treatment approach known as total neoadjuvant therapy(TNT)has gained popularity,in which patients receive both maChT and nCRT prior to resection.We utilized the National Cancer Database to examine temporal trends in TNT usage,and any potential effect on survival.AIM To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation.METHODS We queried the National Cancer Database for patients with locally advanced rectal cancer,Stage II-III,from 2004-2015 treated with nCRT or TNT.TNT was defined as maChT initiated≥90 d prior to nCRT initiation.Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival,with logrank statistics to assess significance.Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias.RESULTS We identified 9066 eligible patients,with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT,respectively.Nodal involvement,stage III disease,and treatment in recent years were predictive of TNT use.There was greater use of TNT with more advanced stage,specifically>1 node involved(odds ratio[OR]=2.88,95%confidence interval[CI]:2.11-3.93,P<0.01)and stage III disease(OR=2.88,95%CI:2.11-3.93,P<0.01).From 2010 to 2012 the use of TNT increased(OR=2.41,95%CI:1.27-4.56,P<0.01)with a greater increase from 2013 to 2015(OR=6.62,95%CI:3.57-12.25,P<0.01).Both the TNT and neoadjuvant chemoradiation arms had a similar 5-year survival at 76%and 78%respectively.Multivariable analysis with propensity score demonstrated that increased age,high comorbidity score,higher grade,African American race,and female gender had worse overall survival.CONCLUSION Our data demonstrates a rising trend in TNT use,particularly in patients with worse disease.Patients treated with TNT and nCRT had similar survival.Randomized trials evaluating TNT are underway.

Impact of postoperative TNM stages after neoadjuvant therapy on prognosis of adenocarcinoma of the gastro-oesophageal junction tumours

AIM To compare prognostic relevance of postoperative tumour/node/metastasis(TMN) stages between patients with and without neoadjuvant treatment. METHODS Data from patients with adenocarcinoma of the gastrooesophageal junction(AEG) who had undergone surgical resection at a single German university centre were retrospectively analysed. Patients with or without neoadjuvant preoperative treatment were selected by exact matching based on preoperative staging. Standard assessment of preoperative(c)TNM stage was based on endoscopic ultrasound and computed tomography of the thorax and abdomen, according to the American Joint Committee on Cancer/Union for International Cancer Control classification system. Patients with cT1cN0cM0 and cT2cN0cM0 stages were excluded from the study, as these patients are generally not recommended for pretreatment. Longterm survival among the various postoperative TNM stages was compared between the groups of patients with or without neoadjuvant treatment. For statistical assessments, a P-value of ≤ 0.05 was considered significant.RESULTS The study included a total of 174 patients. The group of patients who had received preoperative neoadjuvant treatment included more cases of AEG(Siewert) type 1 carcinoma(P < 0.001), and consequently oesophagectomy was performed more frequently among these patients(P < 0.001). The two groups(with or without preoperative neoadjuvant treatment) had comparable preoperative T stages, but the group of patients with preoperative neoadjuvant treatment presented a higher rate of preoperative N-positive disease(P = 0.020). Overall long-term survival was not different between the two groups of patients according to tumours of different AEG classifications, receipt of oesophagectomy or gastrectomy, nor between patients with similar postoperative TNM stage, resection margin and grading. However, an improvement of long-term survival was found for patients with nodal down-staging after neoadjuvant therapy(P = 0.053).CONCLUSION The prognostic relevance of postoperative TNM stages is similar for AEG in patients with or without neoadjuvant preoperative treatment, but treatment-related nodal down-staging prognosticates longer-term survival.

Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

Nomograms for predicting pathological response to neoadjuvant treatments in patients with rectal cancer

BACKGROUND In recent decades, neoadjuvant therapy(NT) has been the standardized treatment for locally advanced rectal cancer(LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response(pCR). If the pathological response(PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore,developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients.AIM To establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC.METHODS Rectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0(ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens(capecitabine/deGramont-RT, mFOLFOX6, and m FOLFOX6-RT) to predict pCR probability.RESULTS Four hundred and three patients were included in this study; 72(17.9%) had pCR at the final pathology report, and 177(43.9%) achieved good downstaging to ypT0-2N0M0(ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia(MRF) status,and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio(NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the m FOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation.CONCLUSION We established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.

Diffusion-weighted magnetic resonance imaging for predicting the response of rectal cancer to neoadjuvant concurrent chemoradiation

AIM:To evaluate the clinical value of diffusion-weighted magnetic resonance imaging(DW-MRI)in predicting the response of rectal cancer to neoadjuvant chemoradiation.METHODS:This prospective study was approved by our institutional review board,and informed consent was obtained from each patient.Fifteen patients(median age 56 years)with locally advanced rectal cancer were treated in our hospital from June 2006 to December 2007.All patients were stageⅢB-C according to the results of MRI and endorectal ultrasound examinations.All patients underwent pelvic irradiation with 45 Gy/25 fx per 35 days.The concurrent chemotherapy regimen consisted of capecitabine 625mg/m2,bid(Monday-Friday),and oxaliplatin 50 mg/m2,weekly.The patients underwent surgery 5-8 wk after the completion of neoadjuvant therapy.T downstaging was defined as the downstaging of the tumor from cT3to ypT0-2 or from cT4 to ypT0-3.Good regression was defined as TRG 3-4,and poor regression was defined as TRG 0-2.Diffusion-weighted magnetic resonance images were obtained prior to and weekly during the course of neoadjuvant chemoradiation,and the apparent diffusion coefficient(ADC)values were calculated from the acquired tumor images.RESULTS:Comparison with the mean pretreatment tumor ADC revealed an increase in the mean tumor ADC during the course of neoadjuvant chemoradiation,especially at the 2ndweek(P=0.004).We found a strong negative correlation between the mean pretreatment tumor ADC and tumor regression after neoadjuvant chemoradiation(P=0.021).In the T downstage and tumor regression groups,we found a significant increase in the mean ADC at the 2ndweek of neoadjuvant therapy(P=0.011;0.004).CONCLUSION:DW-MRI might be a valuable clinical tool to help predict or assess the response of rectal cancer to neoadjuvant chemoradiation at an early timepoint.

Safety and Efficacy of Neoadjuvant DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] Chemotherapy Regimen in Patients with Locally Advanced Gastric and Gastro-Esophageal Junction Cancers: A Single Center Experience from India

Background:?The role of chemotherapy in Gastric Cancer is constantly evolving?with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric cancer (LAGC) namely Platinum based compounds (Cisplatin, Oxaliplatin), Fluoropyrimidines like 5-Flurouracil [(5-FU), Capecitabine)], Taxanes (Docetaxel) and Anthracyclines (Epirubicin). Various doublet and triplet combination chemotherapy regimens have been used for neo-adjuvant chemotherapy (NACT) in LAGCs. In this study we evaluated the safety and efficacy of docetaxel based triplet regimen DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] in LAGC. Material and methods:?50 Newly diagnosed patients of Locally Advanced Gastric Cancer (stage II or III) deemed fit to receive chemotherapy were included in our study. After 3 cycles of neoadjuvant chemotherapy, patients were assessed based on radiological and pathological response.?Results: 50 Patients were included in our study of which majority were male (32), median age at presentation was 55 years and 24 patients presented with a history of gastrointestinal reflux disease (GERD). The most common hematological toxicities observed in our study were anemia (61.2%), neutropenia (42.6%, febrile neutropenia constituted 6%) and thrombocytopenia (13.2%). The most common gastro-intestinal [GI] toxicities observed in our study included nausea (69.2%), vomiting (31.2%), diarrhea (34%), oral mucositis (14%) and constipation (6.6%). We found that safety profile of DOF regimen was favorable with majority of patients tolerating the regimen well. The Overall Response Rate (68%), Disease Control Rate (96%) and Resectability Rate (80%) were higher compared to western studies. Pathological CR (17.5%), ypN0?disease status (42.5%) and nodal down staging (52%), all showed positive correlations with survival outcomes. Conclusion:?DOF regimen is an effective and feasible option for neoadjuvant treatment of LAGC in an Indian population.

Isolation and identification of adipose-derived stromal/stem cells from breast cancer patients after exposure neoadjuvant chemotherapy

BACKGROUND With recent research advances,adipose-derived stromal/stem cells(ASCs)have been demonstrated to facilitate the survival of fat grafts and thus are increasingly used for reconstructive procedures following surgery for breast cancer.Unfortunately,in patients,following radiation and chemotherapy for breast cancer suggest that these cancer treatment therapies may limit stem cell cellular functions important for soft tissue wound healing.For clinical translation to patients that have undergone cancer treatment,it is necessary to understand the effects of these therapies on the ASC's ability to improve fat graft survival in clinical practice.AIM To investigate whether the impact on ASCs function capacity and recovery in cancer patients may be due to the chemotherapy.METHODS ASCs were isolated from the cancerous side and noncancerous side of the breast from the same patients with receiving neoadjuvant chemotherapy(NAC)or notreceiving NAC.ASCs were in vitro treated with 5-fluorouracil(5-FU),doxorubicin(DXR),and cyclophosphamide(Cytoxan)at various concentrations.The stem cells yield,cell viability,and proliferation rates were measured by growth curves and MTT assays.Differentiation capacity for adipogenesis was determined by qPCR analysis of the specific gene markers and histological staining.RESULTS No significant differences were observed between the yield of ASCs in patients receiving NAC treatment and not-receiving NAC.ASCs yield from the cancerous side of the breast showed lower than the noncancerous side of the breast in both patients receiving NAC and not-receiving NAC.The proliferation rates of ASCs from patients didn’t differ much before and after NAC upon in vitro culture,and these cells appeared to retain the capacity to acquire adipocyte traits simile to the ASCs from patients not-receiving NAC.After cessation and washout of the drugs for another a week of culturing,ASCs showed a slow recovery of cell growth capacity in 5-FU-treated groups but was not observed in ASCs treated with DXR groups.CONCLUSION Neoadjuvant therapies do not affect the functioning capacity of ASCs.ASCs may hold great potential to serve as a cell source for fat grafting and reconstruction in patients undergoing chemotherapy.

Stage and size using magnetic resonance imaging and endosonography in neoadjuvantly-treated rectal cancer

AIM: To assess the stage and size of rectal tumours using 1.5 Tesla (1.5T) magnetic resonance imaging (MRI) and three-dimensional (3D) endosonography (ERUS). METHODS: In this study, patients were recruited in a phaseⅠ/Ⅱ trial of neoadjuvant chemotherapy for biopsy-proven rectal cancer planned for surgical resection with or without preoperative radiotherapy. The feasibility and accuracy of 1.5T MRI and 3D ERUS were compared with the histopathology of the fixed surgical specimen (pathology) to determine the stage and size of the rectal cancer before and after neoadjuvant chemotherapy. A Philips Intera 1.5T with a cardiac 5-channel synergy surface coil was used for the MRI, and a B-K Medical Falcon 2101 EXL 3D-Probe was used at 13 MHz for the ERUS. Our hypothesis was that the staging accuracy would be the same when using MRI, ERUS and a combination of MRI and ERUS. For the combination, MRI was chosen for the assessment of the lymph nodes, and ERUS was chosen for the assessment of perirectal tissue penetration. The stage was dichotomised into stageⅠ and stage Ⅱ or greater. The size was measured as the supero-inferior length and the maximal transaxial area of the tumour. RESULTS: The staging feasibility was 37 of 37 for the MRI and 29 of 36 for the ERUS, with stenosis as a limiting factor. Complete sets of investigations were available in 18 patients for size and 23 patients for stage. The stage accuracy by MRI, ERUS and the combination of MRI and ERUS was 0.65, 0.70 and 0.74, respectively, before chemotherapy and 0.65, 0.78 and 0.83, respectively, after chemotherapy. The improvement of the post-chemotherapy staging using the combination of MRI and ERUS compared with the staging using MRI alone was significant (P = 0.046). The post-chemotherapy understaging frequency by MRI, ERUS and the combination of MRI and ERUS was 0.18, 0.14 and 0.045, respectively, and these differences were non-significant. The measurements of the supero-inferior length by ERUS compared with MRI were within 1.96 standard deviations of the difference between the methods (18 mm) for tumours smaller than 50 mm. The agreement with pathology was within 1.96 standard deviations of the difference between imaging and pathology for all tumours with MRI (15 mm) and for tumours that did not exceed 50 mm with ERUS (22 mm). Tumours exceeding 50 mm in length could not be reliably measured by ERUS due to the limit in the length of each recording. CONCLUSION: MRI is preferable to use when assessing the size of large or stenotic rectal tumours. However, staging accuracy is improved by combining MRI with ERUS.

Effect of laparoscopic surgery combined with neoadjuvant chemotherapy on serum CEA, VEGF, CA724, CA242, LEP and T lymphocyte subsets in patients with low rectal cancer

Objective: To study the effect of laparoscopic surgery combined with neoadjuvant chemotherapy on serum CEA, VEGF, CA724, CA242, LEP and T lymphocyte subsets in patients with low rectal cancer. Methods A total of 80 patients with low rectal cancer in our hospital from June 2014 to June 2017 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with laparoscopic surgery, the treatment group were treated with laparoscopic surgery combined with neoadjuvant chemotherapy, and both the two groups were treated for 6 periods with neoadjuvant chemotherapy after surgery. The serum CEA, VEGF, CA724, CA242, LEP levels and peripheral blood CD3+, CD4+, CD8+, NK cells of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum CEA, VEGF, CA724, CA242, LEP levels and peripheral blood CD3+, CD4+, CD8+, NK cells of the two groups before treatment. The serum CEA, VEGF, CA724, CA242 and LEP levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.The peripheral blood CD3+, CD4+, CD8+, NK cells of the two groups of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly higher than the control group. Conclusion: Laparoscopic surgery combined with neoadjuvant chemotherapy can significantly reduce the serum CEA, VEGF, CA724, CA242, LEP levels, improve the immunologic function, and it was worthy clinical application.

Predictive factors of histological response of colorectal liver metastases after neoadjuvant chemotherapy

BACKGROUND Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy(NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases(CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria.More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade(TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.AIM To analyze the predictive factors of the histological response, according to the TRG, on CRLM surgery performed after NAC.METHODSFrom January 2006 to December 2013, 150 patients who had underwent surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG.Based on their TRG, each patient was either assigned to the responder(R) group(TRG 1, 2, and 3) or to the non-responder(NR) group(TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.RESULTS Seventy-four patients were classified as responders and 76 as non-responders.The postoperative mortality rate was 0.7%, with a complication rate of 38%.Multivariate analysis identified five predictive factors of histological response.Three were predictive of non-response: More than seven NAC sessions, the absence of a radiological response after NAC, and a repeat hepatectomy(P <0.005). Two were predictive of a good response: A rectal origin of the primary tumor and a liver-first strategy(P < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr.The factors contributing to a poor prognosis for disease-free survival were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC(P < 0.005).CONCLUSION A non-radiological response and a number of NAC sessions > 7 are the two most pertinent predictive factors of non-histological response(TRG 4 or 5).

Portal vein stenosis after pancreatectomy following neoadjuvant chemoradiation therapy for pancreatic cancer

Extrahepatic portal vein (PV) stenosis has various causes, such as tumor encasement, pancreatitis and as a postsurgical complication. With regard to post-pancreaticoduodenectomy, intraoperative radiation therapy with/ without PV resection is reported to be associated with PV stenosis. However, there has been no report of PV stenosis after pancreatectomy following neoadjuvant chemoradiation therapy (NACRT). Here we report the cases of three patients with PV stenosis after pancreatectomy and PV resection following gemcitabine-based NACRT for pancreatic cancer and their successful treatment with stent placement. We have performed NACRT in 18 patients with borderline resectable pancreatic cancer since 2005. Of the 15 patients who completed NACRT, nine had undergone pancreatectomy. Combined portal resection was performed in eight of the nine patients. We report here three patients with PV stenosis, and thus the ratio of post-operative PV stenosis in patients with PV resection following NACRT is 37.5% in this series. We encountered no case of PV stenosis among 22 patients operated with PV resection for pancreatobiliary cancer without NACRT during the same period. A relationship between PV stenosis and NACRT is suspected, but further investigation is required to determine whether NACRT has relevance to PV stenosis.

Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy

AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.

A retrospective clinical study of neoadjuvant chemotherapy for advanced epithelial ovarian cancer

Objective The aim of this study was to investigate the clinical efficacy of neoadjuvant chemotherapy(NACT) and the prognostic factors for advanced epithelial ovarian cancer(EOC).Methods We enrolled 241 patients with stage III and IV EOC who were diagnosed at the Yunnan Cancer Hospital between October 2006 and December 2015.The observation(NACT-IDS) group(n = 119) received 1–3 courses of platinum-based NACT,followed by interval debulking surgery(IDS) and 6–8 courses of postoperative chemotherapy.The control group underwent primary debulking surgery(PDS)(n = 122) followed by 6–8 courses of postoperative chemotherapy.We analyzed the general conditions of the operations and the survival of both groups.Results Operating time,intraoperative blood loss and postoperative hospitalization were significantly lower in the NACT-IDS group(P < 0.05).The rate of optimal cytoreductive surgery was significantly higher in the NACT-IDS group(P < 0.05).A visible residual lesion was observed in 49(41.18%) and 48(40%) cases in the NACT-IDS and PDS groups,respectively,which were not significantly different(P > 0.05).The percentage of International Federation of Gynecology and Obstetrics(FIGO) stage IV tumors and the recurrence rates were significantly higher in the NACT-IDS group(P < 0.05).The mortality rates were 45.19%(47/104) and 35.19%(38/108) in the NACT-IDS and PDS groups,respectively(P > 0.05).Progression-free survival was 23.75 ± 9.98 and 23.57 ± 12.25 months in the NACT-IDS and PDS groups,respectively(P > 0.05).Overall survival(OS) was 31.11 ± 15.66 and 29.63 ± 18.00 months in the NACTIDS and PDS groups,respectively(P > 0.05).Optimal cytoreductive surgery with or without residual lesion was an independent influencing factor for advanced EOC in multivariate analysis.OS of patients treated with ≥8 courses of chemotherapy was significantly longer than those treated with < 8 courses.Conclusion NACT could improve the intra-and postoperative conditions in advanced EOC patients.Although the percentage of FIGO stage IV cancer was significantly higher in the NACT-IDS group,the prognosis was similar in both the NACT-IDS and PDS groups,suggesting that NACT improves the clinical outcome of advanced EOC.Optimal cytoreductive surgery with no residual lesion is a long-term protective factor in advanced EOC.At least 8 courses of chemotherapy overall or ≥ 6 courses postoperatively improves the OS.

Neoadjuvant radiotherapy for rectal cancer management

Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.

How reliable is current imaging in restaging rectal cancer after neoadjuvant therapy?

In patients with advanced rectal cancer,neoadjuvant chemo radiotherapy provides tumor downstaging and downsizing and complete pathological response in up to 30%of cases.After proctectomy complete pathological response is associated with low rates of local recurrence and excellent long term survival.Several authors claim a less invasive surgery or a non operative policy in patients with partial or clinical complete response respectively,however to identify patients with true complete pathological response before surgical resection remains a challenge.Current imaging techniques have been reported to be highly accurate in the primary staging of rectal cancer,however neoadjuvant therapy course produces deep modifications on cancer tissue and on surrounding structures such as overgrowth fibrosis,deep stroma alteration,wall thickness,muscle disarrangement,tumor necrosis,calcification,and inflammatory infiltration.As a result,the same imaging techniques,when used for restaging,are far less accurate.Local tumor extent may be overestimated or underestimated.The diagnostic accuracy of clinical examination,rectal ultrasound,computed tomography,magnetic resonance imaging,and positron emission tomography using 18F-fluoro-2’-deoxy-Dglucose ranges between 25%and 75%being less than 60%in most studies,both for rectal wall invasion and for lymph nodes involvement.In particular the ability to predict complete pathological response,in order to tailor the surgical approach,remains low.Due to the radio-induced tissue modifications,combined with imaging technical aspects,low rate accuracy is achieved,making modern imaging techniques still unreliable in restaging rectal cancer after chemo-radiotherapy.

Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection

Patients with metastasized carcinoma of the pancreas have a very poor prognosis, and long-term survival cannot be expected. This case report describes two patients with an initial diagnosis of metastatic pancreatic cancer, both with hepatic metastases and one with an additional peritoneal carcinomatosis. Initially, both patients were treated intravenously with the FOLFIRINOX chemotherapy regimen, consisting of 5-FU, folinic acid, irinotecan and oxaliplatin. Surprisingly, the FOLFIRINOX treatment resulted in complete resolution of the hepatic metastases in both patients, with no lesions detectable by computed tomography scan. Furthermore, treatment response included decreased diameter of the primary tumor in the tail of the pancreas and disappearance of the additional peritoneal carcinomatosis. Both patients were discussed by our multidisciplinary tumor board, which recommended surgical resections of the carcinoma. The R0 resection of the primary tumor was successful in both cases and, interestingly, the resected tissues showed no evidence of the hepatic metastases intraoperatively. In the first case, the patient received a postoperative 6-mo course of adjuvant chemotherapy with gemcitabine. In the second case, the patient continued to receive the FOLFIRINOX regimen for an additional 6 mo postoperatively. At 12 mo after the operation, a nonresectable retroperitoneal lymph node metastasis was detected in the first patient, whereas the second patient remained in complete remission at the time of this report(5 mo after the adjuvant therapy was discontinued). This case report is the first of its kind to describe two cases of hepatic metastatic pancreatic carcinoma that were resectable following treatment with FOLFIRINOX. Further studies are required to examine the role of FOLFIRINOX as a neoadjuvant treatment option in subgroups of patients with initially metastasized pancreatic carcinoma.

Fat clearance and conventional fixation identified ypN0 rectal cancers following intermediate neoadjuvant radiotherapy have similar long-term outcomes

BACKGROUND As a prognostic factor for colorectal cancer,lymph node(LN)status,particularly the number of LN harvested,has been demonstrated to be essential in the evaluation of quality control in terms of surgical specimen.Neoadjuvant chemoradiation,however,decreases the LN harvest.Therefore,certain approaches(such as fat clearance or methylene blue)has drawn significant attention in order to raise LN yield.AIM To compare the long-term oncologic outcome of ypN0 rectal cancer identified using fat clearance(FC)or conventional fixation(CF)following 30 Gy in 10 fractions(30 Gy/10f)of neoadjuvant radiotherapy(nRT).METHODS Three hundred and eighty-two patients with resectable and locally advanced rectal cancer were treated by 30 Gy/10f intermediate nRT(biologically equivalent dose of 36 Gy)plus total mesorectal excision.Two specimen fixation methods(FC or CF)were non-randomly used.The ypN0 status was identified in 124 and 101 patients in the FL and CF groups,respectively.Primary endpoints were local recurrence-free survival(LRFS)and cancer-specific survival(CSS).RESULTS The median follow-up of patients was 5.1 years.The median numbers of retrieved LNs in the FC and CF groups were 19.5(range,4-47)and 12(range,0-44),respectively,with a significant difference(P=0.000).The percentages of patients with 12 or more retrieved nodes were 82.3%and 50.5%(101/159)in the FC and CF groups,respectively,with a significant difference(P=0.000).The LRFS at 5 years were 95.7%and 94.6%in the FC and CF groups,respectively,without statistical difference(P=0.819).The CSS at 5 years were 92.0%and 87.2%in the FC and CF groups,respectively,without statistical difference(P=0.482).CONCLUSION For patients with ypN0 rectal cancer who underwent 30 Gy/10f preoperative radiotherapy,the increased retrieval of LNs using fat clearance is not associated with survival benefit.This time-consuming fixation method has a low efficacy as a routine practice.

Magnetic resonance imaging for diagnosis and neoadjuvant treatment evaluation in locally advanced rectal cancer:A pictorial review

High-resolution pelvic magnetic resonance imaging(MRI) is the primary method for staging rectal cancer.MRI is highly accurate in the primary staging of rectal cancer;however,it has not proven to be effective in restaging,especially in complete response evaluation after neoadjuvant therapy.Neoadjuvant chemoradiotherapy produces many changes in rectal tumors and on adjacent area,as a result,local tumor extent may not be accurately determined.However,adding diffusion-weighted sequences to the standard approach can improve diagnostic accuracy.In this pictorial review,an overview of the situation of MRI in the staging and re-staging of rectal cancer is exhibited as a pictorial assay.An experience-and literature-based discussion of limitations and difficulties in interpretation are also presented.

Decrease in the Ki67 index during neoadjuvant chemotherapy predicts favorable relapse-free survival in patients with locally advanced breast cancer

Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.

Unnecessity of lymph node regression evaluation for predicting gastric adenocarcinoma outcome after neoadjuvant chemotherapy

BACKGROUND Neoadjuvant chemotherapy has been applied worldwide to improve the survival of patients with gastric adenocarcinoma(GAC). The evaluation of histological regression in primary tumors is valuable for predicting prognosis. However, the prognostic effect of regression change in lymph nodes(LNs) remains unclear.AIM To confirm whether the evaluation of regression change in LNs could predict the prognosis of GAC patients who received neoadjuvant chemotherapy followed by surgery.METHODS In this study, we evaluated the histological regression of resected LNs from 192 GAC patients(including those with esophagogastric junction adenocarcinoma)treated with neoadjuvant chemotherapy. We classified regression change and residual tumor in LNs into four groups:(A) true negative LNs with no evidence of a preoperative therapy effect,(B) no residual metastasis but the presence of regression change in LNs,(C) residual metastasis with regression change in LNs,and(D) metastasis with minimal or no regression change in LNs. Correlations between regression change and residual tumor groups in LNs and regression change in the primary tumor, as well as correlations between regression change in LNs and clinicopathological characteristics, were analyzed. The prognostic effect of regression change and residual tumor groups in LNs was also analyzed.RESULTS We found that regression change and residual tumor groups in LNs were significantly correlated with regression change in the primary tumor, tumor differentiation, ypT stage, ypN stage, ypTNM stage, lymph-vascular invasion,perineural invasion and R0 resection status. Regression change and residual tumor groups in LNs were statistically significant using univariate Cox proportional hazards analysis, but were not independent predictors. For patients who had no residual tumor in LNs, the 5-year overall survival(OS) rates were 67.5% in Group A and 67.4% in Group B. For the patients who had residual tumors in LNs, the 5-year OS rates were 28.2% in Group C and 39.5% in Group D.The patients in Groups A+B had a significantly better outcome than the patients in Groups C+D(P < 0.01). No significant differences in survival were found between Groups A and B, or between Groups C and D.CONCLUSION The existence of residual tumor in LNs, rather than regression change in LNs, is useful for predicting the prognosis after neoadjuvant chemotherapy in GAC patients. In practice, it may not be necessary to report regression change in LNs.