nCRT Group Research Articles

Predictors of Pathologic Response After Total Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: A National Cancer Database Analysis.

Purpose/objectivesInduction chemotherapy followed by chemoradiation and surgical resection in rectal cancer, known as total neoadjuvant therapy (TNT), is associated with improved pathologic complete response (pCR) rates. The National Cancer Database was utilized to identify factors associated with pCR and survival following treatment with TNT compared to standard neoadjuvant chemoradiation (nCRT).Materials/methodsThe National Cancer Database was queried from 2004 to 2015 for patients with locally advanced, non-metastatic rectal cancer. We identified 16,299 patients receiving neoadjuvant chemotherapy and radiation followed by definitive surgical resection. Patients were stratified by treatment received, either TNT (n=350) or nCRT (n=15,949). Multivariate binomial regression analysis and propensity matching were used to evaluate predictors of pCR. Kaplan-Meier and Cox multivariate analysis of survival were performed.ResultsMedian follow-up was 38 months vs 53 months in the TNT vs nCRT groups, respectively. There were more patients with T4 or node-positive disease in the TNT group. There was a trend towards improved pCR in the TNT group (p=0.053). Patients achieving pCR had improved 5-year overall survival (OS) of 85.1%. The 5-year OS was not improved for TNT (76.2%) over nCRT (69.9%) (p=0.19). Pelvic nodal pCR was significantly higher in the TNT group (72%). When stratified by clinical stage, patients with cT3 (p=0.038) or cN1 (p=0.049) disease had improved OS with TNT.ConclusionsCompared to nCRT, TNT is correlated with higher rates of complete pelvic nodal clearance in patients with locally advanced rectal adenocarcinoma. The use of TNT showed improved survival in patients with cT3 and cN1 disease, indicating a potential benefit for patients with less advanced disease.

Neoadjuvant chemoradiotherapy followed by lateral pelvic lymph node dissection for rectal cancer patients: A retrospective study of its safety and indications.

There is no consensus on the safety and indications of lateral pelvic lymph node dissection (LPND) for patients with clinical lateral pelvic node metastasis (LPNM) after neoadjuvant chemoradiotherapy (nCRT). We retrospectively analyzed 151 patients who underwent total mesorectal excision (TME) + LPND and divided them into two groups: nCRT group (n = 73) and non-nCRT group (n = 78). Thirty-one (20.5%) patients had LPNM by pathology. The operative time was significantly longer in the nCRT group (291.9 vs. 237.0 min, p < 0.001); however, the two groups had comparable intraoperative blood loss (87.3 vs. 78.9 ml, p = 0.607) and morbidity (19.2% vs. 15.7%, p = 0.537). Additionally, in the nCRT group, multivariate logistic regression analysis showed that poor/mucinous/signet adenocarcinoma (odds ratio [OR] = 6.65, 95% confidence interval [CI] = 1.03-43.03, p = 0.047) and post-nCRT LPN size ≥7 mm (OR = 26.67, 95% CI = 2.87-247.91, p = 0.004) were independent risk factors for pathological LPNM. nCRT before TME + LPND is safe and feasible with a comparably low mortality and acceptable morbidity. Poor/mucinous/signet adenocarcinoma and post-nCRT LPN size ≥7 mm were independent predictive factors of pathological LPNM after nCRT for rectal cancer patients with clinical LPNM, and patients with these characteristics should consider LPND after nCRT.

Morbidity and Mortality of Patients Who Underwent Minimally Invasive Esophagectomy After Neoadjuvant Chemoradiotherapy vs Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) vs neoadjuvant chemotherapy (nCT) for treatment of locally advanced esophageal squamous cell carcinoma (ESCC) remain uncertain given lack of high-level clinical evidence. To compare safety and long-term survival of nCRT followed by minimally invasive esophagectomy (MIE) with that of nCT followed by MIE for patients with locally advanced ESCC. A prospective, multicenter, open-label, randomized clinical trial that compared safety and efficacy of nCRT vs nCT followed by MIE for patients with locally advanced ESCC. From January 1, 2017, to December 31, 2018, 264 patients with ESCC of clinical stages from cT3 to T4aN0 to 1M0 were enrolled. Analysis was performed on an intention-to-treat basis from January 1, 2017, to August 30, 2020. Eligible patients were randomized to the nCRT group (n = 132) or the nCT group (n = 132) by a computer-generated random system. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while 40 Gy of concurrent radiotherapy was added for the nCRT group. At about 6 weeks after neoadjuvant therapy, MIE via thoracoscopy and laparoscopy was performed for the patients in both groups. The primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcome, recurrence-free survival time, and quality of life. Among 264 patients (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years), postoperative morbidity was 47.4% in the nCRT group (54 of 114) and 42.6% in the nCT group (46 of 108), with no significant difference between groups (difference, 4.8%; 95% CI, -8.2% to 17.5%; P = .48). Distribution of the severity of complications was similar between the 2 groups based on Clavien-Dindo classification. The 90-day perioperative mortality rate was 3.5% for the nCRT group (4 of 114) and 2.8% for the nCT group (3 of 108) (P = .94). The R0 resection rates were similar between groups (109 of 112 [97.3%] vs 100 of 104 [96.2%]; P = .92). However, patients in the nCRT group had a higher pathologic complete response (residual tumor, 0%) rate (40 of 112 [35.7%] vs 4 of 104 [3.8%]; P < .001) and a higher rate of negative lymph nodes (ypN0, 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P = .03) than those in the nCT group. One-year overall survival using intention-to-treat analysis was 87.1% in the nCRT group (115 of 132) and 82.6% in the nCT group (109 of 132) (P = .30). Furthermore, deaths caused by tumor progression or recurrence were significantly less in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P = .046); however, deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P = .24). Initial results of the trial showed that nCRT followed by MIE has similar safety to and better histopathologic outcome than nCT followed by MIE for treatment of locally advanced ESCC. ClinicalTrials.gov Identifier: NCT03001596.

Neoadjuvant chemoradiotherapy improves survival in locally advanced adenocarcinoma of esophagogastric junction compared with neoadjuvant chemotherapy: a propensity score matching analysis

BackgroundTo analyze whether neoadjuvant chemoradiotherapy (nCRT) could improve the survival for patients with adenocarcinoma of the esophagogastric junction compared with neoadjuvant chemotherapy (nCT). Both neoadjuvant chemotherapy alone and chemoradiotherapy before surgery have been shown to improve overall long-term survival for patients with adenocarcinoma in the esophagus or esophagogastric junction compared to surgery alone. It remains controversial whether nCRT is superior to nCT.Methods170 Patients with locally advanced (cT3-4NxM0) Siewert II and III adenocarcinoma of the esophagogastric junction (AEG) were treated with neoadjuvant chemotherapy consisting of capecitabine plus oxaliplatin with or without concurrent radiotherapy in the Fourth Hospital of Hebei Medical University. Intensity-modulated radiation therapy (IMRT) was used and delivered in 5 daily fractions of 1.8 Gy per week for 5 weeks (total dose of PTV: 45 Gy). 120 Patients were included in the propensity score matching (PSM) analysis to compare the effects of nCRT with nCT on survival.ResultsWith a median follow-up of 41.2 months for patients alive after propensity score matching analysis, the 1- and 3-year OS were 84.8%, 55.0% in nCRT group and 78.3%, 38.3% in nCT group (P = 0.040; HR = 1.65, 95% CI 1.02–2.69). The 1- and 3-year PFS were 84.9%, 49.2% in nCRT group and 68.3%, 29.0% in nCT group (P = 0.010; HR = 1.80, 95% CI 1.14–2.85). The pathological complete response (pCR) was 17.0% in nCRT group and 1.9% in nCT group (P = 0.030). No significant difference was observed in postoperative complications between the two groups.ConclusionThe nCRT confers a better survival with improved R0 resection rate and pCR rate compared with nCT for the patients with locally advanced AEG.

Influence of neoadjuvant therapy on outcomes in patients with resectable carcinoma of esophagus and gastro-esophageal junction from a tertiary cancer care center in India.

The aim of this study is to compare the outcomes of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT) followed by surgery to upfront surgery (surgery alone) in patients with resectable carcinoma of the esophagus (esophageal cancer [EC]), and gastro-esophageal junction (GEJ) in a limited resource setting. A retrospective analysis of a prospectively maintained database was performed to identify patients (from January 2010 through December 2016) who underwent surgery for EC and GEJ cancers. A total of 454 patients were included and categorized into the following groups: nCT (n = 65), nCRT (n = 152) and upfront surgery (n = 237). Squamous cell carcinoma and adenocarcinoma accounted for two-thirds and one-third of the cases, respectively. nCRT group patients were also noted to have smaller tumors, lower margin positivity and a higher R0 resection rates. With a median follow up of 76 months (35-118 months) improved 5-year overall survival was noted in nCRT group in comparison to nCT and upfront surgery groups (56.5% vs. 34% and 35%, respectively, p = .021). The results of our study demonstrate the beneficial effect of nCRT for patients with EC and GEJ in a limited resource setting. Further studies are required to analyze and promote the benefits of nCRT in limited-resource settings.

Adjuvant therapy in the treatment of resected nonmetastatic gallbladder cancer of stage II-IV: A generalized propensity score analysis.

471 Background: The benefit of adjuvant therapy for gallbladder cancer (GBC) remains controversial due to the limited evidence. The current study was aimed to explore the efficacy of adjuvant therapy in patients with resected non-metastatic GBC and to establish a prognosis model to predict the survival benefit of GCB patients with different adjuvant therapies. Methods: Patients with resected non-metastatic GBC of stage II-IV were selected from the Surveillance, Epidemiology, and End Results database and divided into non-radiotherapy and chemotherapy (NCRT) group, chemotherapy (CT) group, and chemoradiotherapy (CRT) group. Generalized propensity score (GPS) and inverse probability of treatment weighting (IPTW) was used to reduce the imbalances between groups. Nomogram was constructed based on Cox proportional hazard model, and the model was validated for discrimination and calibration. Results: Among the 2689 enrolled patients, 1193 (44.4%) patients were classified as stage II, 1371 (51.0%) as stage III, and 125 (4.6%) as stage IV according to the 8th American Joint Commotion Cancer staging manual. Patients in NCRT, CT, and CRT groups were 1703, 444, and 542 respectively. After the IPTW, absolute standardized differences of baseline characteristics were less than 0.1 both in patients with stage II tumors and with stage III-IV tumors. In patients with GBC of stage II, no significant difference in OS was observed between the three treatment groups (P &gt; 0.05). In patients with GBC of stage III-IV, CT group has a superior OS compared with the NCRT group (P &lt; 0.001), and CRT group has a superior OS compared with the CT(P &lt; 0.001) and NCRT (P &lt; 0.001) group. Sensitivity analysis showed consistent results. A nomogram was constructed for patients with stage III-IV tumors to predict the survival benefit of adjuvant therapies. The C-index was 0.673 (95% CI: 0.654-0.692) in the validation using the training set (diagnosed at 2004-2012) and was 0.707 (95% CI: 0.677-0·739) in the internal validation using the validation set (diagnosed at 2013-2015). The calibration curves indicated that the predicted probability closely corresponded to the actual observation OS. Conclusions: Patients with GBC of stage II could not benefit from adjuvant therapy. Patients with GBC of stage III-IV could benefit from chemotherapy and chemoradiotherapy while chemoradiotherapy provide a superior OS. A nomogram was built to predict the survival benefit of different adjuvant therapies in patients with GBC of stage III-IV.

The Effect of Neoadjuvant Therapies for Patients with Locally Advanced Gastric Cancer: A Propensity Score Matching Study

Background: The aim of this study was to evaluate the effect of neoadjuvant therapies (NAT) on patients with locally advanced gastric cancer (LAGC).Methods: This study retrospectively analyzed LAGC patients treated at the China National Cancer Center between October 2006 and December 2018. All patients included were divided into two groups, NAT followed by surgery (NAT-Surgery) and adjuvant chemotherapy following surgery (Surgery-ACT). Subgroup analysis compared between patients underwent either neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiation (nCRT) was conducted. Propensity score matching (PSM) was implemented to reduce selection bias.Results: In total, 2779 patients were included in this study (494 of NAT-Surgery group and 2285 of Surgery-ACT group). After PSM, the patients in NAT-Surgery group had a significantly longer overall survival (OS) than patients in Surgery-ACT group (P<0.001). Subgroup analysis revealed that grade 3 or 4 adverse events were more frequently observed in nCRT group during neoadjuvant treatment (52.0% in nCRT group vs. 34.0% in nCT group, P=0.010). Pathological complete response (pCR) being achieved in 17.0% after nCRT versus 4.0% after nCT (P<0.001). Patients of the nCRT group obtained better disease-free survival (DFS, P=0.024) and local-recurrence-free survival (LRFS, P=0.014) than patients in nCT group, while there was no significant difference in OS between the two groups.Conclusions: In conclusion, NAT improved survival outcomes among LAGC patients over surgery followed by adjuvant chemotherapy. In comparison with nCT, nCRT resulted in higher pCR rate, better DFS and LRFS, without significantly affecting OS.

252 HETEROGENEITY OF CLINICAL LYMPH NODE INVOLVEMENT (CN+) IN ESOPHAGEAL CANCER: A PERSPECTIVE BASED ON METABOLIC VOLUME

Abstract Esophageal cancer with clinical lymph node involvement (cN+) is a heterogeneous disease. Although the cN+ category is of vital importance, preclinical staging cannot establish the number of positive nodes. In this study, we aimed to measure the heterogeneity of esophageal cancer with cN+ based on metabolic volume. We investigated its influence on the response to neoadjuvant treatment. Methods We retrospectively reviewed the patients received neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy during January 2016 and November 2018. All patients had received baseline 18F-FDG PET/CT. All patients were restaged according to the 8th TNM Staging System. We measured the metabolic tumor volume (MTV, cm3) of the whole body (MTVwb) and the primary tumor (MTVp) on the workstation. We also calculated the difference of MTVwb and MTVp (MTVn) and the ratio of MTVwb and MTVp (MTVratio). Logistic regression was used to determine the association between the heterogeneity and the response to neoadjuvant treatment. Results Among the 102 patients enrolled in this study, 54 patients had clinically suspicious lymph nodes in small diameters with lower uptake (MTVn as 0). The median MTVwb, MTVp, and MTVn of the patients were 22.34 (2.09 to 105.24), 19.62 (1.93 to 98.06), and 0 (0 to 89.00), respectively. In nCT and nCRT groups (all patients), 15 (37.5%) and 38 (61.3%) achieved ypN0, respectively. In nCT and nCRT groups (MTVn as 0), 12 (42.9%) and 20 (76.9%) patients achieved ypN0, respectively. Logistic regression revealed that MTVn (0 vs. &amp;gt;0) was independently associated with ypN status in nCRT group (P = 0.035). Conclusion nCRT compared with nCT achieved more effective disease control. In esophageal cancer treated with nCRT, the heterogeneity of cN+ measured by metabolic volume was associated with ypN status. A prospective study was in demand to further validate the findings. Video none

Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer.

Few studies have compared the survival advantage of complete pathologic response (cPR) achieved through neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) in gastric adenocarcinoma. Our study utilizes a large national cancer database to address this question. This is a retrospective review of patients with clinical stage I to III gastric adenocarcinoma from 2004 to 2013 who received nCT or nCRT. Patients who achieved cPR were selected. Associations were evaluated using Mann-Whitney U and Fisher's exact tests. Survival information was summarized using standard Kaplan-Meier methods, where estimates of the median and 5-year survival rates were estimated with 95% confidence intervals. A total of 413 patients who had cPR were identified. Eighty-four patients received nCT and 329 patients received nCRT. Patients in the nCRT group had higher clinical stage (88.4% vs. 75.0%) and more proximal location of tumors (95.4% vs. 45.2%). The nCT group (n = 84) had a 94% 5-year survival rate, while the nCRT group's (n = 329) rate was 60% (p < 0.001). On Cox regression modeling using a propensity-weighted approach, nCT treatment was an independent predictor of improved overall survival (nCRT vs. nCT; HR 10.44, p < 0.001). The use of nCT leads to a significant increase in overall survival in patients when compared with nCRT for those who achieved cPR in gastric adenocarcinoma. While this study is limited in identifying the cause for this difference in overall survival, this important finding nonetheless requires further investigation and should be considered in the development of future gastric cancer trials.

Improved Outcomes after Reperfusion Therapies for Ischemic Stroke: A "Real-world" Study in a Developing Country.

It is unknown if improvements in ischemic stroke (IS) outcomes reported after cerebral reperfusion therapies (CRT) in developed countries are also applicable to the "real world" scenario of low and middle-income countries. We aimed to measure the long-term outcomes of severe IS treated or not with CRT in Brazil. Patients from a stroke center of a state-run hospital were included. We compared the survival probability and functional status at 3 and 12 months in patients with severe IS treated or not with CRT. From 2010 to 2011, we performed intravenous reperfusion when patients arrived within 4.5 h time-window (IVT group) and after 2011, mechanical thrombectomy (MT) combined or not with intravenous alteplase (IAT group). Those who arrived >4.5 h in 2010-2011 and >6 h in 2012-2017 did not undergo CRT (NCRT group). From 2010 to 2017, we registered 917 patients: 74% (677/917) in the NCRT group, 19% (178/917) in the IVT group and 7% (62/917) in the IAT group. Compared to the NCRT group, IVT patients had a 28% higher (HR: 0.72; 95% CI 0.53-0.96) 3-month adjusted probability of survival and risk of functional dependence was 19% lower (adjusted RR: 0.81; 95% CI 0.73-0.91). For those who underwent MT, the adjusted probability of survival was 59 % higher (HR: 0.41; 95% CI 0.21-0.77) and the risk of functional dependence was 21% lower (adjusted RR: 0.79; 95% CI 0.66-094). These outcomes remained significantly better throughout the first year. CRT led to better outcomes in patients with severe IS in Brazil.

Rectum-preserving surgery after consolidation neoadjuvant therapy or totally neoadjuvant therapy for low rectal cancer: a preliminary report

Objective: To investigate the feasibility and safety of sphincter-preserving surgery after neoadjuvant chemoradiotherapy (nCRT) with consolidation chemotherapy in the interval period or total neoadjuvant therapy (TNT) for low rectal cancer. Methods: A descriptive case series study was carried out. Clinical data of patients with locally advanced low rectal cancer (LALRC) who achieved complete clinical response (cCR) or nearly cCR (near-cCR) after nCRT at the Department of Colorectal Surgery of Fujian Medical University Union Hospital from May 2015 to February 2019 were retrospectively analyzed. Case inclusion criteria: (1) Low rectal adenocarcinoma within 6 cm from the anal verge. (2) After nCRT, tumor presented markedly regression as mucosal nodule or abnormalities, superficial ulcer, scar or a mucosal erythema (< 2 cm); no regional lymph node metastasis or distant metastasis was found in rectal ultrasonography, pelvic MRI and PET-CT; MRI showed obvious fibrosis in the original tumor site; and post-treatment CEA was normal. (3) The patient and the family members adhered to receive the transanal full-thickness local excision with informed consent. (4) When the residual lesions were difficult to detect after nCRT, patients received the watch and wait (W&W) strategy. Exclusion criteria: (1) Before nCRT, pathological results showed poorly differentiated or signet-ring cell carcinoma; lateral lymph node metastasis was suspected. (2) When the residual lesion size was more than 3 cm after nCRT, it was difficult to perform local excision. The consolidation nCRT group received 3-4 cycles of CAPOX regimen (oxaliplatin and capecitabine) or six cycles of mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) combined with the long-course radiotherapy (intensity-modulated radiation therapy with a total dose of 50.4Gy). Patients with concurrent chemotherapy more than or equal to five cycles of CAPOX or eight cycles of mFOLFOX6 were defined as total neoadjuvant therapy (TNT) group. Local resection was recommended for patients who were near-cCR according to modified MSKCC criteria 8-33 weeks after the end of radiotherapy. Patients with a near-cCR, who were judged as ycN0 according to PET-CT and MRI and were ypT0 after local excision, could enter the W&W strategy. Patients with pathologic stage more advanced than ypT1, and those with positive resection margin, or lymphovascular invasion were recommended for salvage radical surgery after local excision. The ypT1 patients with a negative resection margin and without lymphovascular invasion might receive the W&W management carefully if they refused radicalsurgery to sacrifice the sphincter for low rectal cancer. Results: Of 32 patients, 14 were males and 18 were females with the average age of 59 years old. Twenty-three patients underwent consolidation nCRT, and 9 received TNT. The first evaluation after treatments showed 19 cases with cCR and 13 with near-cCR. Twenty-nine patients received local excision while 3 patients with undetectable lesions received W&W policy. Four cases (12.5%) underwent salvage radical surgery with abdominoperineal resection. After local excision, 3 cases underwent salvage radical surgery immediately, and the final pathologic result was ypT3N0, ypT2N0, and ypT2N0 respectively, of whom 2 cases were in the group of consolidation CRT and 1 was in the TNT group. Of these 3 cases, 1 case with an initial cT3 stage showed a pathologic stage of ypT1 and a negative circumferential resection margin after consolidation nCRT and local excision, however, the final pathologic stage was ypT3 with fragmented tumor deposits in the mesorectum after the salvage radical surgery. Meanwhile 1 patient in the TNT group receiving W&W suffered from intraluminal regrowth after 7.4 months follow-up and underwent salvage abdominoperineal resection. One patient in the consolidation nCRT group died of stroke 42.5 months after local resection. Another patient in the TNT group had cerebral metastasis 10 months after the W&W policy, but no local recurrence was found in the pelvic cavity, then received resection of the metastatic tumors. The average follow-up for all the patients was 23 (5-51) months. The cumulative local regrowth rate was 5.0%. The overall survival rate was 85.7%, and the sphincter-preservation rate was increased from 25.0% (28/32) in the original plan to 87.5% (28/32) actually. The 3-year disease-free survival rate was 89.7%. The 3-year organ-preserving survival rate was 85.7%, and the 3-year stoma-free survival rate was 82.5%. At present, 31 patients still survived. Conclusions: After nCRT with consolidation chemotherapy or TNT for low rectal cancer, patients with cCR, ycN0 according to PET-CT and MRI, and ypT0 after local excision, can consider the W&W strategy. Strict patient selection with a near-cCR for local resection and sphincter-preserving strategy can reduce the local regrowth of cancer, and the short-term outcomes are satisfactory.

To what extent should the intestinal be resected proximally after radiotherapy: hint from a pathological view.

BackgroundNeoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one non-irradiated margin reportedly significantly reduces the risk of post-operative anastomotic complications in radiation enteritis. However, the exact scope of radiotherapy on the remaining sigmoid colon remains unknown.MethodsWe evaluated the radiation damage of proximally resected colorectal segments in 44 patients with rectal cancer, who received nCRT followed by conventional resection (nCRT-C, n = 21) or proximally extended resection (nCRT-E, n = 23). The segments from another 13 patients undergoing neoadjuvant chemotherapy (nCT) were used as control. We dissected these samples at a distance of 2 cm between the two adjacent sections. Radiation damage in proximally resected colorectal segments was evaluated using the radiation injury score (RIS) and the concentration and distribution patterns of angiostatin.ResultsCompared to those in the nCT group, the nCRT group showed higher RIS, levels of angiostatin, and proportion of diffuse pattern of angiostatin. With increasing distance from the tumor site, these parameters all gradually decreased; and the differences came to be not significant at the site that is over 20 cm from the tumor. The nCRT-E group showed lower RIS (median: 2 vs 4, P = 0.002) and a greater proportion of non-diffuse angiostatin (87% vs 55%, P = 0.039) at the proximal margins compared with the nCRT-C group.ConclusionsThe severity of the radiation damage of the proximal colon is inversely proportional to the proximal-resection margin length. Little damage was left on the proximal margin that was over 20 cm from the tumor. Removal of an initial length of ≥20 cm from the tumor may be beneficial for rectal-cancer patients after nCRT.

MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial.

Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. nCRT was indicated in patients with positive mrMRF (≤ 1mm) in cT4 and cT3 carcinomas of the lower rectal third. A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%.Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Reliability of clinical nodal status regarding response to neoadjuvant chemoradiotherapy compared with surgery alone and prognosis in esophageal cancer patients

Background: Clinical nodal (cN) staging is a key element in treatment decisions in patients with esophageal cancer (EC). The reliability of cN status regarding the effect on response and survival after neoadjuvant chemoradiotherapy (nCRT) with esophagectomy was evaluated in determining the up- and downstaged pathological nodal (pN) status after surgery alone. Material and methods: From a prospective database, we included all 395 EC patients who had surgery with curative intent with or without nCRT between 2000 and 2015. All patients were staged by a standard pretreatment protocol: 16-64 mdCT, 18 F-FDG-PET or 18 F-FDG-PET/CT and EUS ± FNA. After propensity score matching on baseline clinical tumor and nodal (cT/N) stage and histopathology, a surgery-alone and nCRT group (each N = 135) were formed. Clinical and pathological N stage was scored as equal (cN = pN), downstaged (cN > pN) or upstaged (cN < pN). Prognostic impact on disease free survival (DFS) was assessed with multivariable Cox regression analysis (factors with p value <.1 on univariable analysis). Results: The surgery-alone and nCRT group did not differ in cT/N status. Pathologic examination revealed equal staging (32 vs. 27%), nodal up (43 vs. 16%) and downstaging (25 vs. 56%), respectively (p < .001). Nodal up-staging was common in cT3-4a tumors and adenocarcinomas in the surgery-alone group, while nodal downstaging was found in half of cT1-2 and cT3-4 regardless of tumortype after nCRT. Prognostic factors for DFS were pN (p = .002) and lymph-angioinvasion (p = .016) in surgery-alone, and upper abdominal cN metastases (p = .012) and lymph node ratio (p = .034) in the nCRT group. Conclusions: Despite modern staging methods, correct cN staging remains difficult in EC. Nodal overstaging (cN > pN) occurred more often than understaging impeding an adequate assessment of pathologic complete response and prognosis after nCRT.

Genome-wide copy number alteration (CNA) of circulating cell-free DNA (cfDNA) as a prognostic biomarker in esophageal squamous cell carcinoma (ESCC).

e15582 Background: Although neoadjuvant chemoradiation (nCRT) plus surgery or definitive CRT (dCRT) are the standard treatment for locally advanced ESCC, there are no reliable clinical tools for predicting prognosis or monitoring treatment response for CRT in ESCC. We aimed to identify a biomarker for predicting outcomes using cfDNA in ESCC patients (pts) receiving CRT. Methods: This prospective biomarker study analyzed pretreatment plasma cfDNA from pts with nCRT plus surgery (n = 23) and pts with dCRT for locally advanced ESCC (n = 17) at Asan Medical Center in South Korea from Jul. 2017 to Jun. 2018. Low depth whole-genome sequencing of cfDNA was used to identify CNA and I-score was developed to express genomic instability. I-score was defined as the sum of absolute Z-scores of sequenced reads on each chromosome. Results: The pathologic complete response (pCR) was achieved in 7 pts (30.4%) in the nCRT group, and the clinical complete response (cCR) was achieved in 3 pts (17.6%) and clinical partial response (cPR) in 8 pts (47.1%) in the dCRT. The baseline cfDNA concentrations were no significant association with the clinical T stage (cT 1-2 vs. cT 3-4; 0.27 vs. 0.28 ng/μL; p = 0.752), pathologic response (pCR vs. non-pCR; 0.26 vs. 0.30 ng/μL; p = 0.270), ypT stage (ypT 0-2 vs. ypT 3-4; 0.28 vs. 0.36 ng/μL; p = 0.161) and ypTNM stage (ypTNM 1 vs. ypTNM 2-4; 0.26 vs. 0.36 ng/μL; p = 0.065). When analyzing cfDNA concentration before and after CRT, cfDNA concentration was significantly increased after CRT (0.31 vs. 0.55 ng/μL; p = 0.007). The baseline I-score was not associated with baseline clinical stage, but was significantly associated with ypT stage (ypT 1-2 vs. 3-4; 30.4 vs 839.1; p = 0.009), time to progression (median TTP; 11.8 mo in the I-score-low group vs. 6.1 mo in the I-score-high group; p = 0.036), and overall survival (median OS; not reached vs. 10.4 mo; p = 0.046) in the nCRT group. In the dCRT group, I-score was significantly associated with higher disease progression rate (33.3 vs. 58.8%; p = 0.024) with tendency of distant metastasis (33.5 vs. 57.1%; p = 0.490), and short response duration (median, 5.7 mo in the I-score-high group vs not reached in the I-score-low group). Conclusions: The cfDNA concentration is not a good biomarker for prognostication and monitoring the course of treatment in ESCC pts treated with CRT. But the I-score, an indicator of genomic instability in ctDNA, was a significant predictor of poor prognosis.

Optimal treatment strategy for rectal cancer based on the risk factors for recurrence patterns.

For rectal cancer, multimodality therapeutic approach is necessary to prevent local recurrence and distant metastasis. However, the efficacy of additional treatments, such as neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (NAC), and lateral pelvic lymph node dissection (LPLND), has not been scrutinized. Recurrence patterns were categorized into local recurrence and distant metastasis. Local recurrence was classified into two types: (1) pelvic cavity recurrence and (2) LPLN recurrence. First, we analyzed the risk factors for each recurrence pattern. Second, based on the status of clinically suspected involvement of circumferential resection margin (cCRM), the efficacy of additional treatments was investigated. A total of 240 patients was enrolled. nCRT was performed for 25 (10%), NAC was for 46 (19%), and LPLND was for 35 patients (15%). As the recurrence patterns, pelvic cavity recurrence occurred in 15 (6%), LPLN recurrence in 8 (3%), and distant metastasis in 42 patients (18%). Five-year overall survival and relapse-free survival were 87% and 70%, respectively. Multivariate analysis indicated that pelvic cavity recurrence was associated with cCRM status and tumor histology, that LPLN recurrence was with serum carcinoembryonic antigen level and LPLN swelling, and that distant metastasis was with clinical N category. In the cCRM-positive subgroup (n = 66), cumulative rate of pelvic cavity recurrence was lower in the nCRT group than in the NAC or non-NAC/nCRT group (P = 0.02 and 0.09, respectively). cCRM status was associated with pelvic cavity recurrence, and LPLN swelling was with LPLN recurrence. nCRT could reduce pelvic cavity recurrence in cCRM-positive subgroup.

Impact of radiation dose during neoadjuvant chemoradiation on postoperative complications in esophageal (EC) and gastroesophageal junction cancers (GEJC).

119 Background: Neoadjuvant chemoradiation (nCRT) followed by resection is standard of care for operable stage II-III EC and GEJC; however, it can be associated with significant risk of postoperative complications (POC). The CROSS study group reported no increase in POC severity with nCRT using 41.4 Gy compared to surgery alone as defined by the Comprehensive Complication Index (CCI). We applied the CCI metric to evaluate the impact of nCRT radiation dose of &lt; 50 Gy vs. ≥ 50 Gy on POC rates and compared to the CROSS rates. Methods: We retrospectively reviewed 82 pts (2004-2016) with EC or GEJC treated with nCRT followed by resection at our institution. 29 (35%) pts were treated with &lt; 50 Gy (range 39.6-46.8 Gy) and 53 (65%) were treated with ≥ 50 Gy (range 50.0-52.5 Gy) delivered using IMRT/VMAT (41%), 3D-CRT (46%), or tomotherapy IMRT (12%). Concurrent chemotherapy were carboplatin/paclitaxel (59%), cisplatin/5-FU (17%), or other (24%). Resection was performed by Ivor Lewis esophagectomy (67%), esophagogastrectomy (14%), or trans-hiatal approach (11%). POC within 30 days were graded using the Clavien-Dindo scale and CCI scores were computed and compared between the two dose groups and with the CROSS nCRT group. Results: CCI scores and complication rates between our &lt; 50 Gy and ≥ 50 Gy groups were not significantly different. Assuming a normal distribution of the CROSS CCI scores, there was no significant difference in CCI scores between the CROSS study nCRT, &lt; 50 Gy, or ≥ 50 Gy groups. Rates of pulmonary complications were greater in the CROSS study. Conclusions: In highly selected EC and GEJC pts, definitive nCRT radiation doses do not appear to increase POC rates. Thus, 50 Gy can likely be delivered without increasing toxicity while also achieving a definitive dose for pts not able or willing to undergo subsequent surgery. [Table: see text]

Efficacy analysis of neoadjuvant chemoradiotherapy combined with total pelvic exenteration in the treatment of primary T4b rectal cancer

To investigate the value of neoadjuvant chemoradiotherapy (nCRT) combined with total pelvic exenteration (TPE) in the treatment of primary T4b rectal cancer. A retrospective cohort study was conducted to analyze the clinicopathological data of 31 patients with primary T4b rectal cancer who underwent TPE from January 2008 to December 2015 at Peking University First Hospital. preoperative clinical stage (cTNM) was defined as cT4b primary rectal cancer with only front wall Invasion; the lower edge of tumor was within 10 cm from the anal margin; TPE was performed; R0 resection was confirmed by pathology. Patients with recurrent rectal cancer, distant metastasis, and undergoing TPE for non-rectal tumors were excluded. Patients were divided into nCRT group and non-nCRT group according to whether receiving nCRT before surgery. The nCRT group received long course radiotherapy (total dose 50 Gy in 25 daily fractions) with concomitant chemotherapy (Capecitabine), and the surgery was performed 6-8 weeks after the neoadjuvant chemoradiation, while the non-nCRT group received surgery directly. The intraoperative, postoperative and pathological conditions and local recurrence were compared between the two groups. The survival curves were drawn by Kaplan-Meier method and the survival of two groups were compared. A total of 31 patients were enrolled, including 13 patients in the nCRT group and 18 patients in the non-nCRT group. The baseline data, such as age, duration of disease, preoperative basic disease, body mass index, smoking rate, and tumor distance from the anal margin, were not significantly different between the two groups (all P>0.05). In the nCRT group and non-nCRT group respectively, the ratio of anal preservation was 30.8%(4/13) and 38.9%(7/18) (P=0.468), the median intraoperative blood loss was 1 000 ml and 800 ml (P=0.644), the operation time was (531.7±137.2) minutes and (498.0±90.1) minutes (P=0.703), the median hospital stay was 18 days and 14 days (P=0.400), the morbidity of complications within 30 days after surgery was 23.1%(3/13) and 38.9%(7/18)(P=0.452), the incidence of postoperative abdominal abscess was 15.4%(2/13) and 0 (P=0.168), the proportion of secondary surgery was 7.7%(1/13) and 11.1%(2/18)(P=1.000), whose differences were not significantly different. The proportion of postoperative pathological pT4b in whole group was 58.1%(18/31), including 53.8%(7/13) in nCRT group and 61.1%(11/18) in non-nCRT group, which was not significantly different between the two groups (P=0.691). The number of harvested lymph node in nCRT group was 13.5±5.9, which was significantly less than 23.0±11.8 in non-nCRT group (P=0.013). There was no pathological complete remission (ypCR) case in nCRT group, and among 13 patients, tumor regression grade (TRG) of 2, 3, 4, and 5 was in 1 case (7.7%), 6 cases (46.2%), 5 cases(38.5%), and 1 case (7.7%), respectively. The median follow-up time was 33 (2 to 115) months, and the follow-up rate was 93.5%(29/31). One case was lost in both the nCRT group and non-nCRT group. The 3-year disease-free survival rate was 43.5% in pooled data, and was 43.6% and 43.3% in nCRT group and non-CRT group respectively without significant difference (P=0.833). The 3-year overall survival rate was 51.1% in pooled data, and was 45.7% and 54.7% in nCRT group and non-nCRT group respectively without significant difference (P=0.653).The local recurrence rate of nCRT and non-nCRT groups was 8.3%(1/12) and 5.9%(1/17) respectively, and the distant metastasis rate was 50.0%(6/12) and 41.2%(7/17) respectively, whose differences were not statistically significant as well (P=1.000 and P=0.865, respectively). For primary T4b rectal cancer which can achieve R0 resection through total pelvic exenteration, neoadjuvant chemoradiotherapy has not been demonstrated any advantage in tumor regression, reducing local recurrence, or improving survival, and may increase postoperative complications.

Neoadjuvant or Definitive Chemoradiation for Locoregional Esophageal Cancer and its Outcome at South Egypt Cancer Institute (Retrospective Study)

AbstractBackground: It is well known about esophageal carcinoma, the aggressive and invasive nature, in addition to the poor outcome. The experience of south Egypt cancer institute was to review the locally advanced esophageal carcinoma, treated by chemo radiation either followed by surgery or not, and their outcome.Aim of Study: In this study, we evaluate the efficacy of chemoradiation as a definitive or preoperative treatment.Patients and Methods: During the period June 2008, till June 2014, 55 patients with locally advanced esophageal cancer were reviewed for treatment with preoperative or definitive concurrent chemo radiation, at Radiation Oncology Department, South Egypt Cancer Institute, Assiut University. Statistical analysis of data was done by the statistical package for the social science (SPSS) version 20.Results: Out of 55 patients, 26 patients were included for definitive chemo radiation (dCRT). And 29 patients were included for neoadjuvant chemo radiation (nCRT). Squamous cell carcinoma (SqCC) represented in 72.7% of patients. Patients had disease stage II and III (32.7% and 67.3%) respectively. Median total radiation dose was 50.4 Gy over 28 fractions. Cisplatin+Fluorouracil regimen was received by 30 (54.5%) patients, while Paclitaxel+Carboplatin regimen was received by 25 (45.5%) patients. Overall response (CR+PR) was observed in 34 (72.3%) patients, while disease progression occurred in 5 (10.6%) patients and 17% (8 patients) had stable disease. The disease stage at diagnosis was a significant factor affecting clinical response. Out of 29 patients at neoadjuvant group, 18 patients (62%) underwent surgery, without major postoperative complications. Complete patho-logical response (no residual cancer cells) was observed in 6 (33%) patients. Median OS for dCRT and nCRT was 21 and 39 months respectively, it was in favor for nCRT group with no statistical significance (p-value=0.20). Median PFS for dCRT and nCRT was 16 and 18 months respectively, with no statistical significance (p-value=0.363). Disease stage at diagnosis and clinical response after radiotherapy were very highly significant factors affecting patients' overall survival and disease progression survival (p-value=0.014). Overall grade ³3 toxicity 26 events was observed in 16 (29.0%) of the patients.Conclusion: Neoadjuvant chemo radiation followed by surgery is considered as a standard care management for patients with resectable locally advanced esophageal carcinoma and fit for surgery. For patients with inoperable disease or unfit for surgery, definitive chemo radiation is accepted treatment option. The used chemotherapy regimens, Cispla-tin/Fluorouracil and Paclitaxel/Carboplatin, are tolerable in most patients with acceptable toxicity profile; and with no differences between two regimens.

FA03.05: NEOADJUVANT CHEMOTHERAPY OR CHEMORADIOTHERAPY FOR ADENOCARCINOMA OF THE ESOPHAGUS

Abstract Background Multimodality treatment of patients with esophageal adenocarcinoma (EAC) improve survival, but the optimal treatment strategy remains undetermined. The aim of this study was to compare outcomes in patients undergoing neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT) for EAC. Methods Patients who underwent nCT or nCRT followed by surgery for EAC were identified from a prospective database (2000–2017) and included in this study. After propensity score matching, we compared the impact of the treatments on postoperative complications, in-hospital mortality, pathological outcomes and survival rates. Results Of the 396 eligible patients, 262 patients were analysed following propensity score matching. This resulted in 131 patients in the nCT group versus 131 patients in the nCRT group. There were no significant differences between the nCT and nCRT groups for overall complications (59% vs 57%, P = 0.802) or in-hospital mortality (2% vs 0%, P = 0.156). Patients who had nCRT had more R0 resections (93% vs. 83%, P = 0.013), and a higher pathological complete response rate (15% vs. 5%, P &lt; 0.001). The pattern of recurrence was similar (P = 0.753) and there were no differences in 5-year disease-free survival rates (nCT vs nCRT; 39% vs 39%, P = 0.879) or 5-year overall survival rates (nCT vs nCRT; 44% vs 33%, P = 0.645). Conclusion In this study no differences between nCT and nCRT were seen in postoperative complications and in-hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities. Disclosure All authors have declared no conflicts of interest.