Neoadjuvant Chemoradiotherapy Group Research Articles

Comparable regional therapeutic effects between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy for locally advanced lower rectal cancer in terms of histopathological analysis

Neoadjuvant chemoradiotherapy (NACRT) for lower rectal cancer is commonly used in many Western countries. NACRT improves local control, but it may also induce anal dysfunction, postoperative complications, and late effects associated with radiation. Neoadjuvant chemotherapy (NAC) for lower rectal cancer has recently been employed to improve these problems, but the local control effect of NAC when compared with NACRT is controversial. The aim of the present study was to compare the effects of NAC and NACRT using histopathological analysis. The subjects included 16 patients treated with NAC and 10 patients treated with NACRT prior to surgery. Pathological effects on primary lesions and lymph nodes were evaluated based on fibrosis and tumor depth prior to and following preoperative therapy. In the NAC and NACRT groups, the T downgrade rates were 87.5 and 80%, T depth/F depth ratios were 0.61 and 0.73, pathological T downgrade rates were 25 and 40%, pathological complete response rates were 12.5 and 0% for primary lesions and 33.3 and 37.5% for lymph nodes, and the N conversion rates were 80 and 37.5%. There were no significant differences between the groups. These results suggest that the pathological therapeutic effects of NAC were similar to those of NACRT, and NAC may be effective as an alternative therapy to NACRT.

Short-term Outcomes in Patients with Carcinoma of the Esophagus and Gastroesophageal Junction Receiving Neoadjuvant Chemotherapy or Chemoradiation before Surgery. A Prospective Study.

BackgroundNeoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NACRT) have been demonstrated to improve survival compared to surgery alone in esophageal carcinoma, but the evidence is scarce on which of these therapies is more beneficial, particularly with regard to resectability rates, postoperative morbidity and mortality, and histological responses.ObjectiveThis study compares the resectability, pathological response rates, and short-term surgical outcomes in patients with carcinoma of the esophagus or gastroesophageal junction receiving NACT or NACRT prior to surgery.MethodsPatients with resectable carcinoma of the esophagus or gastroesophageal junction adenocarcinoma, squamous cell carcinoma, and adenosquamous histologies were enrolled in this well-matched prospective non-randomized study. Thirty-five patients were given NACT, and 35 NACRT. In the NACT group, 25 patients received three cycles of three-weekly carboplatin and paclitaxel, and 10 received three cycles of cisplatin/5-fluorouracil, while all the patients in the NACRT group received 41.4 Gy of radiotherapy concomitant with five cycles of weekly paclitaxel and carboplatin-based chemotherapy.ResultsTwenty-two patients in the NACT group and 33 patients in NACRT group had resection (P value = 0.0027). The percentage of microscopically margin-negative resection (R0 resection) was similar in both the groups (86% versus 88%). The incidences of surgical and non-surgical complications were similar in both the groups (P=0.34). There was no 30-day mortality. There was a trend toward more pathological complete regression in the NACRT group (P=0.067). The percentage of patients achieving complete tumor regression at the primary site (pT0) was significantly higher in the NACRT group. The down-staging effect on nodal status was similar in both the groups (P=0.55). There was a statistically significant reduction in tumor size in the NACRT group. The median numbers of nodes harvested and positive nodes were similar in both the groups.ConclusionPatients receiving NACRT had better resectability rates and pathological response rates, but similar postoperative morbidity compared to the NACT group.

Neoadjuvant Chemotherapy Versus Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma.

To confirm the superiority of neoadjuvant chemoradiotherapy (NACRT) over neoadjuvant chemotherapy (NAC) as preoperative therapy for locally advanced esophageal cancer. A total of 298 patients with resectable esophageal cancer were initially enrolled; 62 patients received NAC and 236 patients received NACRT. Propensity score matching was applied to create a study cohort. Postoperative 30-day mortality rate, overall postoperative complication rate, and overall survival time did not differ between those groups. Complete pathological response occurred in one patient treated with NAC and 16 treated with NACRT (p<0.001). In patients with borderline-resectable T4 disease, overall survival was superior in the NACRT group compared to that in the NAC group (p=0.040). No survival advantage was observed between NAC and NACRT groups. Limited to patients with borderline-resectable T4, NACRT achieved a higher rate of primary tumor volume reduction and R0 resection, and a more favorable prognosis compared to NAC.

PS01.134: WHERE TO START? COMPARING INDUCTION CHEMORADIOTHERAPY AND UPFRONT SURGERY IN THE TREATMENT OF CLINICAL T2N0 ESOPHAGEAL CANCER

Abstract Background The purpose of this study was to evaluate the survival difference in clinical T2N0 esophageal cancer patients receiving neoadjuvant chemoradiotherapy (CRT) vs. upfront surgery. Methods Between 1/1/1995 to 12/31/2012, a prospectively maintained database was used to identify patients with cT2N0 esophageal adeno- and squamous cell carcinoma. Exclusion criteria included: lack of endoscopic esophageal ultrasonographic (EUS) staging, incomplete resection, and prior treatment with endoscopic mucosal or submucosal resection. Cox-proportional hazard ratios were used to compare the primary outcomes of overall (OS) and disease-free survival (DFS). Secondary outcomes included: rate of postoperative complications, rate of pathologic upstaging/response, and induction/adjuvant treatment completion rate. Pre-hoc subgroup analysis compared pathologically upstaged patients receiving upfront surgery followed by adjuvant chemotherapy to those treated with neoadjuvant CRT. Results A total of 161 cT2N0 esophageal cancer patients were identified based on EUS staging. Upfront surgery was offered to 134 patients (83%), with 27 patients (17%) receiving induction CRT. Univariate analysis did not demonstrate any significant baseline differences between the two groups. In the upfront surgery group, 53 (39.6%), 28 (20.9%) and 53 (39.6%) patients were pathologically down-staged, accurately staged and upstaged respectively. Upstaging was higher in the upfront surgery group (53/134, 39.6% vs. 4/27, 14.8%; P = 0.02), while 11/27 (40.7%) patients receiving neoadjuvant CRT demonstrated complete pathologic response. Of those eligible for adjuvant chemotherapy, only 21/55 (38.2%) received treatment. In the neoadjuvant CRT group, 51.9% completed all planned therapy, compared to 23.6% of patients treated with upfront surgery followed by adjuvant chemotherapy (P = 0.01). Cox proportional hazard ratio did not demonstrate an advantage to induction CRT in terms of OS (HR = 1.64, P = 0.43) or DFS (HR = 1.36, P = 0.69). In general, patients with pathologic upstaging had worse OS (HR = 2.73, P = 0.001) and DFS (HR = 4.18, P = 0.003). Conclusion EUS was only accurate in staging T2N0 patients in 20.9% of cases. While neoadjuvant CRT did not confer a survival advantage, these results likely reflect the low number of patients being referred for induction therapy. Neoadjuvant CRT was however associated with lower rates of pathologic upstaging and higher rates of treatment completion. Further research should evaluate the survival outcomes in pathologically upstaged cT2N0 patients not receiving neoadjuvant therapy. Disclosure All authors have declared no conflicts of interest.

Neoadjuvant chemotherapy with or without neoadjuvant radiotherapy compared with neoadjuvant chemoradiotherapy for esophageal cancer.

Although it was controversial for treating locally advanced resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy (NACR) was more widely accepted rather than neoadjuvant chemotherapy (NAC) worldwide. With the development of paclitaxel, a high response rate to NAC was reported in many studies. Our hypothesis is that lots of patients could get a response from NAC alone and avoid unnecessary NACR. Those who had no response from NAC could still response from the followed radiotherapy. We attempted to circumvent the controversy over the use of NAC, NACR and made a combined version, NAC ± neoadjuvant radiotherapy (NAR). The retrospective study compared NAC ± NAR with NACR between June 30, 2015 and October 31, 2016. Sixty consecutive borderline resectable ESCC were included: thirty-one in NAC ± NAR group and 29 in NACR group. The toxicities, response rates, operative data, complications, length of stay, and overall survival (OS) rates were evaluated. The response rate to NAC ± NAR was 93.5%; to NACR was 86.2%. There was no grade 3-4 non-hematologic adverse events after NAC ± NAR, but three in the NACR group. Arrhythmias (6.5% vs. 37.9%, P=0.003), pneumonitis (25.8% vs. 51.7%, P=0.039) and anastomotic leakage (0% vs. 13.8%, P=0.049) were more likely in NACR group. Postoperative hospitalization stays were significantly prolonged in the NACR (9 vs. 16 d, P<0.001). A point estimate of the 2-year OS rate of the NAC ± NAR group was 84.0%, the NACR group 80.7% (P=0.410). Compared with NACR, the NAC ± NACR provided the same survival benefits but low post operation complication rate. In the future, it might be a choice for locally advanced ESCC.

Abstract 4762: Clinicopathologic findings of borderline resectable pancreatic cancer after neoadjuvant chemoradiotherapy

Abstract BACKGROUND: The resection rate and survival period of resectable pancreatic ductal adenocarcinoma (PDAC) have increased gradually. Unfortunately, only 15-20% of patients have resectable disease at diagnosis, with the remainder presenting with distant metastatic or locally advanced tumors. Borderline resectable PDAC (BR-PDAC) is defined as a tumor that involves the portal vein (PV) and/or superior mesenteric vein (SMV), and has low resectability. However, there are many practical advantages to neoadjuvant chemoradiotherapy (NAC-RT) for BR-PDAC. Although the clinical effects of NAC-RT in BR-PDAC have been discussed, only a few studies have reported pathological features. We herein studied the effect of NAC-RT on the histological features of BR-PDAC. MATERIALS AND METHODS: Tissue samples of 14 patients with BR-PDAC undergoing NAC-RT (NAC-RT group; male: 7 patients, female: 7 patients; average age:64.8+8.1 years) and 78 patients with conventional PDAC (control group), resected at the Kurume University Hospital were obtained. The BR-PDACs had PV and/or SMV invasion at initial clinical diagnosis. All patients with BR-PDAC underwent NAC-CRT, comprising chemotherapy and external beam irradiation (50.4 Gy). The microvessel invasion (MVI), lymphovascular invasion (LVI), neural invasion (NI), portal vein invasion (PVI), extrapancreatic plexus invasion (PLI), and TNM classification in the surgical specimens were examined. All statistical analyses were performed using StatMate IV (ATMS, Tokyo, Japan). All statistical tests were two-tailed, and P &amp;lt; 0.05 was considered statistically significant. RESULTS: The distribution of stages in the NAC-RT group was as follows: stage IA (n = 5, 36%), IIA (n = 6, 43%), IIB (n = 3, 21%). The pathological grade was determined to be G1 in 9 cases (64%), G2 in 4 cases (28%) and G3 in 1 case (8%). The difference in average tumor size between the NAC-RT and control groups was significant (P&amp;gt; 0.001). Lymph node metastases were significantly infrequently observed in the NAC-RT group compared with the control (P=0.009). The NAC-RT group had a significant lower MVI (29%, 4/14) and LVI (57%, 8/14) than the control group (MVI: P&amp;lt;0.001, LVI: P=0.011). However, there was no significant difference in NI (P=0.129). Ten patients without PVI and /or PLI in the NAC-RT group (71%) had significantly better prognosis than those in the control group (P=0.029), although there was no significant difference in overall survival rates between both groups (P=0.100). CONCLUSIONS: NAC-RT might be more advantageous by inhibiting local invasion, hematogenous and lymphatic metastasis, and could contribute to a better prognosis in patients with BR-PDAC, partly due to the prevention of PVI and/or PLI in pancreatic cancer. Citation Format: Yoshiki Naito, Masamichi Nakayama, Hiroto Ishikawa, Kenjiro Takahashi, Toru Hisaka, Koji Okuda, Masaru Fukahori, Yusuke Ishida, Yoshinobu Okabe, Yutaro Mihara, Masahiko Tanigawa, Jun Akiba, Takuji Torimura, Hirohisa Yano. Clinicopathologic findings of borderline resectable pancreatic cancer after neoadjuvant chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4762.

Clinical impact of laparoscopic intersphincteric resection following neoadjuvant chemoradiotherapy for locally advanced rectal cancer: case-controlled study

Background: Recently, laparoscopic (Lap) intersphincteric resection (ISR) for low-lying rectal cancer is gradually permeating worldwide. However, the usefulness of Lap-ISR after neoadjuvant chemoradiotherapy (NCRT) has not been clarified. This retrospective study aimed to evaluate the feasibility of Lap-ISR after NCRT for locally advanced low-lying rectal cancer. Methods: Fourteen patients with primary locally low-lying rectal cancer were enrolled in this study and underwent curative Lap-ISR between January 2008 and December 2011. Seven patients underwent Lap-ISR after NCRT (NCRT group) and seven patients underwent Lap-ISR without NCRT (non-NCRT group). Patient characteristics, short-term outcomes, postoperative anal function, and long-term oncological outcomes were evaluated and compared between the groups. Results: The tumor diameter was significantly larger in the NCRT group than the non-NCRT group (38±7 and 28±9 mm, respectively; P=0.04) and cStage was significantly more advanced in the NCRT group than the non-NCRT group (P=0.02). There were no significant differences in operative data or postoperative course between the groups. The Wexner score measured 5 years after initial surgery was significantly higher the NCRT group than the non-NCRT group (8.8±4.1 and 4.6±1.9, respectively; P=0.04). There were no significant differences in local recurrence rate, distant recurrence rate, or cancer-specific death rate between the two groups (median follow-up period was 60 months). Conclusions: Lap-ISR after NCRT is a feasible treatment option based on short-term outcomes, long-term oncological outcomes, and postoperative anal function. These data suggest that Lap-ISR after NCRT may be an appropriate treatment option for locally advanced low-lying rectal cancer.

Clinical impact of laparoscopic intersphincteric resection following neoadjuvant chemoradiotherapy for locally advanced rectal cancer: case-controlled study

Background: Recently, laparoscopic (Lap) intersphincteric resection (ISR) for low-lying rectal cancer is gradually permeating worldwide. However, the usefulness of Lap-ISR after neoadjuvant chemoradiotherapy (NCRT) has not been clarified. This retrospective study aimed to evaluate the feasibility of Lap-ISR after NCRT for locally advanced low-lying rectal cancer. Methods: Fourteen patients with primary locally low-lying rectal cancer were enrolled in this study and underwent curative Lap-ISR between January 2008 and December 2011. Seven patients underwent Lap-ISR after NCRT (NCRT group) and seven patients underwent Lap-ISR without NCRT (non-NCRT group). Patient characteristics, short-term outcomes, postoperative anal function, and long-term oncological outcomes were evaluated and compared between the groups. Results: The tumor diameter was significantly larger in the NCRT group than the non-NCRT group (38±7 and 28±9 mm, respectively; P=0.04) and cStage was significantly more advanced in the NCRT group than the non-NCRT group (P=0.02). There were no significant differences in operative data or postoperative course between the groups. The Wexner score measured 5 years after initial surgery was significantly higher the NCRT group than the non-NCRT group (8.8±4.1 and 4.6±1.9, respectively; P=0.04). There were no significant differences in local recurrence rate, distant recurrence rate, or cancer-specific death rate between the two groups (median follow-up period was 60 months). Conclusions: Lap-ISR after NCRT is a feasible treatment option based on short-term outcomes, long-term oncological outcomes, and postoperative anal function. These data suggest that Lap-ISR after NCRT may be an appropriate treatment option for locally advanced low-lying rectal cancer.

Neoadjuvant Chemoradiotherapy for Patients with cT3/Nearly T4 Esophageal Cancer: Is Sarcopenia Correlated with Postoperative Complications and Prognosis?

Since the clinical impact of sarcopenia on multimodal therapy for patients with esophageal cancer is not well understood, this study was conducted to determine the influence of sarcopenia on the efficacy of neoadjuvant chemoradiotherapy (NACRT) for locally advanced esophageal cancer. The skeletal muscle index was quantified at the level of the third lumbar vertebra on computed tomography images, and sarcopenia was defined as a skeletal muscle index that was less than the average for each gender. We compared treatment outcomes in patients with cT3 and nearly T4 thoracic esophageal squamous cell carcinoma between the sarcopenia group (n=85) and the non-sarcopenia group (n=72). The 5-year survival rates were 33.4% in the non-sarcopenia group and 31.5% in the sarcopenia group; these differences were not significant. The prognosis of the patients with sarcopenia was worse than that of the patients without sarcopenia in the surgery-alone group, but there was no difference between patients with and without sarcopenia in the NACRT group. NACRT could be a useful option for patients with locally advanced esophageal squamous cell carcinoma, even for those with sarcopenia, without increasing the incidence of morbidity and mortality.

Perioperative and long-term impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer.

367 Background: Although much attention has been paid to neoadjuvat treatment for pancreatic cancer (PC), its efficacy remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred sixty patients who preoperatively received full-dose gemcitabine (1000 mg/m2) with concurrent radiation of 54 Gy between 2006 and 2016 were analyzed. One hundred thirty patients who underwent upfront surgery were served as control. Results: Among the 160 patients treated with NACRT, 153 patients (96%) completed the protocol treatment. The reasons of failure to complete NACRT were drug-induced pneumonia, acute mucosal injury, severe cholangitis and poor performance status (PS). Furthermore 21 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 9 patients, tumor progression in 7 and poor PS in 5. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group compared to the control group (P = 0.033, P = 0.002). Furthermore, the rate of lymph node metastasis, R0 resection and pathological stage were favorable in the NACRT group (P &lt; 0.0001, P = 0.006, P &lt; 0.0001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.015). Importantly, patients treated with NACRT had a better prognosis than those without (median survival time: 60.2 vs. 28.5M, P = 0.008). In addition, according to tumor resectability status, patients were classified as R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) groups. As a result, patients treated with NACRT had a better prognosis than those without in the R and BR-P groups (58.6 vs. 34.2M, P = 0.013, 62.4 vs. 18.8M, P = 0.015), while NACRT had no significant impact on prognosis in the BR-A group. Conclusions: Neoadjuvant chemoradiotherapy may have a variety of favorable impact in pancreatic cancer treatment. Furthermore, NACRT may improve the prognosis especially in resectable and borderline resectable pancreatic cancer with venous involvement.

Neoadjuvant chemoradiotherapy of pancreatic cancer induces a favorable immunogenic tumor microenvironment associated with increased major histocompatibility complex class I-related chain A/B expression.

Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer. Resected specimens were analyzed for the presence of DAMPs, major histocompatibility complex class I-related chain A/B (MICA/B), and CD8+ TILs, CD4+ TILs, and forkhead box P3 positive (Foxp3+ ) TILs. The Treg/TIL ratio was obtained by dividing the number of Foxp3+ TILs, a surrogate for regulatory T cells, by the sum of CD8+ and CD4+ TILs. Overexpression of calreticulin, Hsp70, and MICA/B were all significantly correlated with NACRT administration. In the NACRT group, high MICA/B expression was associated with a low Treg/TIL ratio, indicating a favorable immunogenic tumor microenvironment. Patients with a lower Treg/TIL ratio had longer survival. Overexpression of MICA/B, a component of DAMPs induced by NACRT, may play an important role in acquiring a favorable immune response for pancreatic cancer which contributes to longer survival, suggesting the potential of immunotherapy of this recalcitrant disease, especially for patients with overexpression of DAMPs.

Comparison of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in treating locally advanced esophageal squamous cell carcinoma

Objective To compare the efficacy of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT) in treating locally advanced esophageal squamous cell carcinoma. Methods We retrospectively analyzed a total of 177 patients who received NCRT (72 patients) or NCT (105 patients) combined with surgery for esophageal squamous cell carcinoma from January 2009 to October 2015 in the Affiliated Cancer Hospital of Zhengzhou University. The survival rate was analyzed using the Kaplan-Meier method. Results Among the 177 patients (clinical stage cT2-4N0-1M0), the 2-and 3-year sample sizes were 44 and 26 in the NCRT group, and 47 and 28 in the NCT group. The pathological complete response (pCR) rate was significantly higher in the NCRT group than in the NCT group (22% vs. 10%, P=0.019). There were no significant differences in the incidence of postoperative complications, mortality, and recurrence rate between the two groups (all P>0.05). The 2-and 3-year overall survival rates for the NCRT group were 74% and 51%, versus 64% and 51% for the NCT group (P=0.527); the 2-and 3-year disease-free survival rates for the NCRT group were 54% and 50%, versus 54% and 46% for the NCT group (P=0.379). Conclusions Compared with NCT, NCRT significantly increases the pCR rate without increasing postoperative complications and mortality in esophageal squamous cell carcinoma patients. However, since the survival rate is similar between the two groups, the efficacy of NCRT and NCT remains to be verified by further prospective, multi-centered, and large-sample studies. Key words: Esophageal neoplasms/chemotherapy; Esophageal neoplasms/chemoraidotherapy; Adjuvant chemoradiotherapy; Prognosis

Neoadjuvant chemoradiotherapy (NCRT) compared with chemotherapy (NCT) in locally advanced squamous-cell cancer of the esophagus.

202 Background: Neoadjuvant chemotherapy with or without radiotherapy are the common treatments for locally advanced squamous-cell esophageal cancer(ESCC). There is no sufficient data to choose between these two effective therapies. The aim of our retrospective study was to compare the clinical efficacy between these two strategies of complete pathological response (pCR), postoperative morbidity, mortality, and overall and disease-free survival in patients with locally advanced ESCC. Methods: Patients with stage T2-4N0-1M0 squamous-cell esophageal cancer at our institution were recruited, including patients who underwent NCRT (1 cycle of cisplatin and 5-fluorouracil with concurrent radiotherapy) or NCT (2 cycles of cisplatin and 5-fluorouracil only ) before esophagectomy. Results: From January 2009 to October 2015, a total of 177 patients were analyzed, with 72 received NCRT and the remaining 105 received NCT. The pathological complete response (pCR) rate was 22.2% (n = 16) in NCRT group and 9.5% (n = 10) in NCT group ( P= 0.019). The postoperative mortality was 1.4% in NCRT group, versus 4.8% in NCT group. The postoperative morbidity was 20.8% in NCRT group, versus 27.6% in NCT group. There was no significant difference in recurrence between the two groups ( P= 0.397). 1-,2-,3-year overall survival rates in NCRT and NCT group were 87%, 74%, 51% and 81%, 64%, 51%, respectively ( P= 0.527), and 1-,2-,3-year DFS rates were 77%, 54%, 50% and 65%, 54%, 46%, respectively( P= 0.379). Conclusions: For patients with locally advanced squamous-cell esophageal cancer, the addition of radiotherapy to neoadjuvant chemotherapy may result in higher complete pathological response with acceptable postoperative mortality and morbidity, while the long-term survival benefit is not significant.

Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment.

440 Background: Combined arterial resection during pancreatectomy can be a challenging treatment, and outcome would be more favorable if the tumor becomes technically removable from the artery. Neoadjuvant chemoradiotherapy (NACRT) is expected to achieve locoregional control and enable margin-negative resection. To investigate the effects of NACRT in patients with pancreatic adenocarcinoma (PDAC) which were deemed borderline resectable through preoperative imaging due to abutment of the major artery, including the superior mesenteric artery (SMA) or common hepatic artery (CHA), but were still considered to be technically removable. Methods: Comparisons were make between 71 patients who underwent upfront surgery and 21 patients who underwent NACRT followed by surgery in the strategy to preserve the artery, using unmatched and inverse probability of treatment weighting analysis (UMIN000017115). Results: Fifty patients in the upfront surgery group and 18 in the NACRT group underwent curative resection (70% vs 86%, respectively; P = 0.1609). The results of the propensity score weighted logistic regressions indicated that the incidences of pathological lymph node metastasis and a pathological positive resection margin were significantly lower in the NACRT group (odds ratio, 0.006; P &lt; 0.0001 and odds ratio, 0.007; P = 0.0005, respectively). Among the propensity-score matched patients, the estimated 1- and 2-year survival rates in the upfront surgery group were 66.7% and 16.0%, respectively, and those in the NACRT group were 80.0% and 65.2%, respectively. Conclusions: It was suggested that chemoradiotherapy followed by surgery provided clinical benefits in patients with PDACs in contact with the SMA or CHA. Clinical trial information: 000017115.

Factors predictive of receiving neoadjuvant versus adjuvant chemoradiotherapy in locally advanced rectal cancer and the impact on overall survival.

686 Background: Neoadjuvant chemoradiotherapy (NCRT) is generally accepted as the optimal treatment strategy compared to adjuvant chemoradiotherapy (ACRT) for locally advanced rectal cancer due to improvement in local control and reduced toxicity. However, NCRT has not been shown to improve overall survival (OS). We investigated the effect of NCRT versus ACRT on OS as well as the impact of demographic factors and clinical stage for the selection of each treatment approach utilizing the National Cancer Data Base. Methods: Adult patients with stage II and stage III adenocarcinoma of the rectum diagnosed from 2004-2013 were included. Chi-square analysis was used to compare demographic variables and clinical stage between the NCRT and ACRT treatment groups. Univariate and multivariate logistic regression modeling was used to identify factors predictive of each treatment strategy. Kaplan Meier and log-rank analysis along with propensity score matching was performed to determine the effect on OS. Results: A total of 20,262 patients were identified: 17,737 (87.5%) received NCRT and 2,525 (12.5%) received ACRT. Utilization of NCRT increased over the study period (p &lt; 0.01). Factors associated with receipt of NCRT on multivariate analysis include: treatment at an academic institution (OR 0.76, 95% CI 0.68-0.85), income greater than $46,000 (OR 0.79, 95% CI 0.67-0.92), and living greater than 50 miles from a treatment facility. Factors associated with receipt of ACRT on multivariate analysis include: female sex (OR 1.12, 95% CI 1.01-1.24), Charlson comorbidity index of 1 (OR 1.18, 95% CI 1.04-1.34), and radiotherapy dose greater than 5040 centigray (OR 1.76, 95% CI 1.56-1.98). Compared to ACRT, NCRT was associated with a decreased risk of death on multivariate analysis (HR 0.91, 95% CI 0.84-1.00), which persisted after propensity score analysis. Conclusions: The use of NCRT for locally advanced rectal cancer is increasing and is associated with an OS benefit compared to ACRT.

Inverse Probability of Treatment Weighting Analysis of Upfront Surgery Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Pancreatic Adenocarcinoma with Arterial Abutment.

Combined arterial resection during pancreatectomy can be a challenging treatment, and outcome would be more favorable if the tumor becomes technically removable from the artery. Neoadjuvant chemoradiotherapy (NACRT) is expected to achieve locoregional control and enable margin-negative resection. To investigate the effects of NACRT in patients with pancreatic adenocarcinoma (PDAC) which were deemed borderline resectable through preoperative imaging due to abutment of the major artery, including the superior mesenteric artery (SMA) or common hepatic artery (CHA), but were still considered to be technically removable. In the current study, comparisons were make between 71 patients who underwent upfront surgery and 21 patients who underwent NACRT followed by surgery in the strategy to preserve the artery, using unmatched and inverse probability of treatment weighting analysis (UMIN000017115). Fifty patients in the upfront surgery group and 18 in the NACRT group underwent curative resection (70% vs 86%, respectively; P = 0.16). The results of the propensity score weighted logistic regressions indicated that the incidences of pathological lymph node metastasis and a pathological positive resection margin were significantly lower in the NACRT group (odds ratio, 0.006; P < 0.001 and odds ratio, 0.007; P < 0.001, respectively). Among the propensity-score matched patients, the estimated 1- and 2-year survival rates in the upfront surgery group were 66.7% and 16.0%, respectively, and those in the NACRT group were 80.0% and 65.2%, respectively. In conclusion, it was suggested that chemoradiotherapy followed by surgery provided clinical benefits in patients with PDACs in contact with the SMA or CHA.

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial

Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84·1 months (range 61·1-116·8, IQR 70·7-96·6), median overall survival was 48·6 months (95% CI 32·1-65·1) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months (14·2-33·7) in the surgery alone group (HR 0·68 [95% CI 0·53-0·88]; log-rank p=0·003). Median overall survival for patients with squamous cell carcinomas was 81·6 months (95% CI 47·2-116·0) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months (15·4-26·7) in the surgery alone group (HR 0·48 [95% CI 0·28-0·83]; log-rank p=0·008); for patients with adenocarcinomas, it was 43·2 months (24·9-61·4) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months (13·0-41·2) in the surgery alone group (HR 0·73 [95% CI 0·55-0·98]; log-rank p=0·038). Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. Dutch Cancer Foundation (KWF Kankerbestrijding).

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer.

Much attention has been paid to preoperative treatment as a new strategy especially for borderline resectable pancreatic cancer (BRPC). The purpose of this study was to define the optimal indication of neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer. We analyzed consecutive 184 patients who had undergone pancreatic resection in Nara Medical University Hospital. Resectability status was classified by NCCN guidelines. Full-dose gemcitabine with concurrent radiation was used as NACRT. We evaluated 85 patients treated with NACRT in comparison with 99 patients without NACRT as control. The regimen of NACRT was well tolerated and feasible. The perioperative outcomes were almost comparable. The postoperative complications were significantly less frequent in NACRT group than non-NACRT group. The pathological effects on both resectable and borderline tumors were favorable in NACRT group compared to non-NACRT group. The overall survival of resectable pancreatic cancer was significantly better than that of BRPC regardless of whether the patients were treated with or without NACRT. The prognosis of the patients with NACRT in resectable tumors was significantly better than without, while there was no significant difference in BRPC. Furthermore, multivariate analysis of various factors in the patients with NACRT identified resectability status and completion of adjuvant chemotherapy as independent prognostic factors. NACRT did not improve the prognosis of the patients with BRPC, although it induced substantial pathological antitumor effect. In contrast, the prognosis of resectable pancreatic cancer treated with NACRT was favorable. Therefore, resectable pancreatic cancer may be good indication for multimodal treatment including NACRT.

Immunohistochemical analysis of cancer stem cell markers in pancreatic adenocarcinoma patients after neoadjuvant chemoradiotherapy.

BackgroundCancer stem cells (CSCs) have been reported to play an important role in chemoradiation resistance. Although the association of CSC markers with clinicopathological outcomes after neoadjuvant chemoradiotherapy (NACRT) has been reported in various types of cancers, there have been no such reports for pancreatic cancer. Here we examined the sequential changes in CSC marker expressions after NACRT in patients with pancreatic adenocarcinoma (PA) and the impact of these changes on the prognosis.MethodsWe used immunohistochemistry to evaluate the expressions of the CSC markers epithelial cell adhesion molecule (EpCAM), CD24, CD44, CD133, CXCR4 and Aldehyde dehydrogenase 1 (ALDH1) in resected specimens obtained from 28 PA patients, and we compared these expressions with the patients’ clinicopathological parameters and survival data.ResultsThe expression frequencies of CD44 and ALDH1 were significantly higher in the NACRT group (n = 17) compared to the non-NACRT group (n = 11), but the CD133 expression was significantly lower in the NACRT group. In the NACRT group, the expression of CD133 was inversely correlated with that of ALDH1, and CD133+/ALDH1- expression was associated with an unfavorable patient outcome.ConclusionThis is the first report showing that NACRT may influence the expression frequencies of CD44, CD133 and ALDH1 in PA patients. Moreover, CD133 and ALDH1 expressions may be useful predictors of prognosis in PA patients who have received NACRT.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-687) contains supplementary material, which is available to authorized users.

Efficacy of modified neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A single institution experience in Taiwan

Background: Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision is now recommended for patients with locally advanced rectal cancer (LARC). This retrospective study was aimed to analyze the treatment efficacy in LARC patients in a single institute. Materials and Methods: Rectal cancer patients with clinically T3, T4, or nodal positive (N1-2) diseases who received either NCRT or adjuvant chemoradiotherapy (ACRT) were retrospectively enrolled between 2007 and 2011. The treatment outcome and clinical characteristics of study population were compared. Results: There were 176 patients been enrolled with a mean age of 63.1 years. Totally, 123 (69.9%) patients received NCRT and 53 (30.1%) patients received ACRT, respectively. The median duration of follow-up was 43.3 months in NCRT group and 47.6 months in ACRT group. There was no significant difference about overall survival (OS), progression-free survival (PFS), and local relapse-free survival (LRFS) between two treatment groups. However, NCRT achieved pathological complete remission (pCR) of 27.6%. In addition, the patients with pathologically downstage after NCRT (the responders) had significantly better PFS (P ＜ 0.0001), local RFS (P=0.0468), and OS (P=0.0045), compared with non-responder after NCRT. Oxaliplatin-based NCRT did not significantly increase treatment response, OS and PFS, compared with other regimens in our analysis (P=0.29). Conclusions: In our cohort, NCRT achieved high pCR rate than those reported in previous literature. Although there was no significant improvement of OS, PFS, and LRFS in NCRT group, there was a significant improvement of LRFS, OS, and PFS in those responders after NCRT.