Long-Term Total Neoadjuvant Therapy Leads to Impressive Response Rates in Rectal Cancer: Results of a German Single-Center Cohort.

Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy-TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II-III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials.

Clinical Relevance of Lateral Pelvic Lymph Node Dissection for Enlarged Lateral Nodes in Locally Advanced Low Rectal Cancer without Preoperative Treatment.

Objectives: The present study aimed to investigate the clinical relevance of lateral pelvic lymph node dissection (LPLND) in low rectal cancer without preoperative treatment, with a focus on the presence of LPLN enlargement in preoperative imaging. Methods: Consecutive patients with cT3 to T4 low rectal cancer who underwent mesorectal excision and LPLND without preoperative treatment between 2007 and 2018 at a single dedicated cancer center were included. LPLN short-axis diameter (SAD) measured using preoperative multi-detector row computed tomography (MDCT) was evaluated retrospectively. Results: A total of 195 consecutive patients were analyzed. Overall, 101 (51.8%) and 94 (48.2%) patients had visible and no visible LPLNs in preoperative imaging, including 56 (28.7%), 28 (14.4%), and 17 (8.7%) patients had SADs of <5 mm, 5-7 mm, and ≥7 mm, respectively. Incidence of pathologically confirmed LPLN metastasis were 18.1%, 21.4%, 28.6%, and 52.9%, respectively. Overall, thirteen (6.7%) patients developed local recurrence (LR), including one patient who developed lateral recurrence, yielding a 5-year cumulative risk for LR of 7.4%. Five-year RFS and OS for all patients were 69.7% and 85.7%, respectively. No differences were observed in the cumulative risk for LR and OS between any pairs of groups. Conclusions: No significant difference was observed in the cumulative risk for LR and OS regardless of LPLN SAD, implying the good impact of LPLND on the prevention of lateral recurrence, as well as the difficulty of predicting LPLN metastasis using only LPLN SAD in preoperative imaging.

Metastasis risk stratification and response prediction through dynamic viable circulating tumor cell counts for rectal cancer in a neoadjuvant setting.

PURPOSE: Distant metastasis (DM) and neoadjuvant treatment response prediction remain critical challenges in the management of locally advanced rectal cancer (LARC). The aim of this study was to investigate the clinical relevance of viable circulating tumor cells (CTCs) for DM or response in patients with LARC in a neoadjuvant setting. METHODS: The detection of viable CTCs at different stages of treatment was planned for consecutive patients from a prospective trial. The Kaplan-Meier method, Cox proportional hazards model, and logistic regression model were utilized to analyze factors associated with DM or pathological complete response (pCR) and clinical complete response (cCR). RESULTS: Between December 2016 and July 2018, peripheral blood samples from 83 patients were collected before any treatment (median follow-up time, 49.3 months). CTCs were present in 76 of 83 patients (91.6%) at baseline, and more than three CTCs detected in the blood sample was considered high risk. Only the CTC risk group was significantly associated with 3-year metastasis-free survival (MFS) (high risk vs. low risk, 57.1% (95% CI, 41.6-72.6) vs. 78.3% (95% CI, 65.8-90.8), p = 0.018, log-rank test). When all the important variables were entered into the Cox model, the CTC risk group remained the only significant independent factor for DM (hazard ratio (HR), 2.74; 95% CI, 1.17-6.45, p = 0.021). The pCR and continuous cCR rates were higher in patients with a decreased number of CTCs of more than one after radiotherapy (HR, 4.00; 95% CI, 1.09-14.71, P = 0.037). CONCLUSIONS: The dynamic detection of viable CTCs may strengthen pretreatment risk assessment and postradiotherapy decision making for LARC. This observation requires further validation in a prospective study.

Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure?

BACKGROUND: Some patients with even T2 low rectal cancer are known to develop lateral pelvic lymph node metastasis. This study aimed to investigate real-world evidence regarding lateral nodal metastasis on T2 low rectal cancer treatment. METHODS: Consecutive patients with pathological T2 low rectal adenocarcinoma who underwent curative-intent surgery between January 2007 and December 2015 at two Japanese cancer centres dedicated to lateral pelvic lymph node dissection were identified and included in the analysis. Lateral pelvic lymph node metastasis was defined as pathologically confirmed metastatic lateral pelvic lymph node or lateral-local recurrence after primary surgery. RESULTS: A total of 215 consecutive patients, including 101 and 114 patients who did and did not undergo bilateral lateral pelvic lymph node dissection, were included in the analysis. Overall, 19 (8.8%) patients had lateral pelvic lymph node metastasis, including 13 with pathologically confirmed metastatic lateral pelvic lymph node and six with lateral-local recurrence. A total of 10 (4.7%) patients had local recurrence, including six with lateral-local recurrence, two with central-local recurrence and two with anastomotic recurrence. Five/7-year cumulative risks of lateral-local recurrence in patients with and without lateral pelvic lymph node dissection were 1.1/1.1% and 3.9/5.2%, respectively. CONCLUSION: The problem of the relatively high rate of lateral local recurrence remains in treating T2 low rectal cancer with only total mesorectal excision. The selection of high-risk patients of lateral pelvic lymph node metastasis and the indication of additional treatment in T2 low rectal cancer should be discussed further.

DUPAN-II normalisation as a biological indicator during preoperative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). METHODS: This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. RESULTS: Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039). CONCLUSION: Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.

Does Loosening the Inclusion Criteria of the CROSS Trial Impact Outcomes in the Curative-Intent Trimodality Treatment of Oesophageal and Gastroesophageal Cancer Patients?

AIM: To determine the efficacy of preoperative chemoradiotherapy as per the CROSS protocol for oesophageal/gastroesophageal junction cancer (OEGEJC), when expanded to patients outside of the inclusion/exclusion criteria defined in the original clinical trial. MATERIALS AND METHODS: Data were collected retrospectively on 229 OEGEJC patients referred for curative-intent preoperative chemoradiotherapy. Outcomes including pathological complete response (pCR), overall survival (OS), cancer-specific survival and recurrence-free survival (RFS) of patients who met CROSS inclusion criteria (MIC) versus those who failed to meet criteria (FMIC) were determined. RESULTS: In total, 42.8% of patients MIC, whereas 57.2% FMIC; 16.6% of patients did not complete definitive surgery. The MIC cohort had higher rates of pCR, when compared with the FMIC cohort (33.3% versus 20.6%, P = 0.039). The MIC cohort had a better RFS, cancer-specific survival and OS compared with the FMIC cohort (P = 0.006, P = 0.004 and P = 0.009, respectively). Age >75 years and pretreatment weight loss >10% were not associated with a poorer RFS (P = 0.541 and 0.458, respectively). Compared with stage I-III patients, stage IVa was associated with a poorer RFS (hazard ratio (HR) = 2.158; 95% confidence interval (CI) = 1.339-3.480, P = 0.001). Tumours >8 cm in length or >5 cm in width had a trend towards worse RFS (HR = 2.060; 95% CI = 0.993-4.274, P = 0.052). CONCLUSION: Our study showed that the robust requirements of the CROSS trial may limit treatment for patients with potentially curable OEGEJC and can be adapted to include patients with a good performance status who are older than 75 years or have >10% pretreatment weight loss. However, the inclusion of patients with celiac nodal metastases or tumours >8 cm in length or >5 cm in width may be associated with poor outcomes.

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BACKGROUND: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. METHODS: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. DISCUSSION: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.

Preoperative oncologic therapy and the prolonged risk of venous thromboembolism in resectable pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most prothrombotic cancers. Among patients receiving preoperative chemotherapy followed by surgery, chemotherapy and surgery represent a compound risk for venous thromboembolism (VTE), rendering the postoperative time a period of interest. We aimed to analyze whether preoperative oncologic therapy increases the risk for VTE after surgery and identify which characteristics associate with VTE. METHODS: We first identified patients surgically treated for pancreatic cancer at Helsinki University Hospital between 2000 and 2017, collecting the following data: gender, age at surgery, preoperative medication, body mass index (BMI), preoperative chemo(radio)therapy, tumor size, positive node ratio, perineural and perivascular invasion, tumor grade, surgical technique, postoperative anticoagulation, adjuvant therapy, time of VTE, time of local disease recurrence, time of distant metastasis, and time of death. With a follow-up period of at least 2 years or until death, we compared a total of 93 preoperative oncologic therapy and 291 upfront surgery patients (n = 384, median age 66.5 years). RESULTS: Preoperative oncologic therapy increased the risk for thrombosis after surgery (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.03-2.53). The VTE incidence rate remained high for up to 2 years after surgery. BMI ≥30 kg/m2 , prior anticoagulation, and disease recurrence (p < 0.05, respectively) associated with VTE. VTE is also associated with shorter overall survival (HR 3.25; 95% CI 2.36-4.44). In 71.6% (95% CI 60.5-81.1) of patients, VTE was diagnosed after disease recurrence. CONCLUSIONS: Preoperative oncologic therapy represents an independent risk factor for VTE, not only during the immediate postoperative period but up to 2 years after surgery. VTE is associated with obesity, prior anticoagulation, and disease recurrence and diminishes overall survival.

Risk Factors for Anorectal Dysfunction After Interspincteric Resection in Patients With Low Rectal Cancer.

Purpose: The objective of this study was to explore the risk factors for anorectal dysfunction after intersphincteric resection in patients with low rectal cancer. Methods: A total of 251 patients who underwent intersphincteric resection from July 2014 to June 2020 were included in this study, for which the Kirwan's grade, Wexner score, and anorectal manometric index were used to evaluate the anorectal function and other parameters including demographics, surgical features, and clinical and pathological characteristics. These parameters were analysed to explore the potential risk factors for anorectal function after intersphincteric resection. Results: In the 251 included patients, 98 patients underwent partial intersphincteric resection, 87 patients underwent subtotal intersphincteric resection, and 66 patients underwent total intersphincteric resection. There were 53 (21.1%) patients who had postoperative complications, while no significant difference was observed between the three groups. Furthermore, 30 patients (45.5%) in the total intersphincteric resection group were classified as having anorectal dysfunction (Kirwan's grade 3-5), which was significantly higher than that in the partial intersphincteric resection group (27.6%) and subtotal intersphincteric resection group (29.9%). The mean Wexner score of patients that underwent total intersphincteric resection was 7.9, which was higher than that of patients that had partial intersphincteric resection (5.9, p = 0.002) and subtotal intersphincteric resection (6.4, p = 0.027). The initial perceived volume was lower in the total intersphincteric resection group than in the partial and subtotal intersphincteric resection groups at 1, 3, and 6 months after intersphincteric resection. In addition, the resting pressure, maximum squeeze pressure, and maximum tolerated volume in the total intersphincteric resection group were worse than those in the partial and subtotal groups at 3 and 6 months after intersphincteric resection. Univariate and multivariate analyses suggested that an age ≥65, total intersphincteric resection, and preoperative chemoradiotherapy were independent risk factors for anorectal dysfunction (P = 0.023, P = 0.003, and P = 0.008, respectively). Among the 66 patients who underwent total intersphincteric resection, 17 patients received preoperative chemoradiotherapy, of which 12 patients (70.6%) were classified as having anorectal dysfunction. Conclusion: The current study concluded that age ≥65, total intersphincteric resection, and preoperative chemoradiotherapy were risk factors for anorectal dysfunction after intersphincteric resection. The morbidity of anorectal dysfunction after total intersphincteric resection for patients who received preoperative chemoradiotherapy was relatively high, and the indication should be carefully evaluated.

The immunological impact of preoperative chemoradiotherapy on the tumor microenvironment of pancreatic cancer.

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse-free survival (odds ratio = 2.37; P = .033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT.

Evaluation and treatment results of trimodality therapy for advanced esophageal squamous cell carcinoma.

OBJECTIVES: The prognosis for highly advanced esophageal squamous cell carcinoma (ESCC) remains poor, and there is currently no standard treatment. The purpose of this study was to examine the benefits of trimodality therapy [chemoradiation plus surgery, (CRT + S)] by evaluating the surgical outcomes of patients with ESCC in Keiyukai Sapporo Hospital, Japan. We assessed the preoperative and postoperative adverse events, treatment effects of preoperative CRT, metastatic diagnosis of the dissected lymph nodes, and survival. PATIENTS AND METHODS: Between 2012 and 2018, 148 patients with highly advanced ESCC who underwent preoperative CRT + S were analyzed for diagnosis and staging, preoperative complications, clinical and histopathological effects of CRT in the resected specimens, survival rates, and recurrences. RESULTS: The grade 3 and higher complications of preoperative CRT were neutropenia in 3 cases and thrombocytopenia in 1 case. Among the postoperative complications, there were 2 cases (1.4%) of direct surgical death, only tracheobronchial bleeding and liver failure. Using the 11th edition of the classification of esophageal cancer by the Japanese Esophageal Society, 60 patients (40.5%) were classified as grade 3 (negative for cancer cells, pathological complete response). However, 20 of them (33.3%) had metastatic tumor cells in the lymph nodes. The overall 5-year survival rate was 58.5%. Including references to the pathological findings and recurrence patterns, there is no effective diagnostic method for selecting the subsequent approach based on the effectiveness of CRT. CONCLUSION: Planned surgery following CRT was the only solution for achieving better treatment results. CRT + S is a promising treatment with low direct surgical mortality.

Short-term outcomes of preoperative chemoradiotherapy with S-1 for locally advanced rectal cancer.

The purpose of the present study was to evaluate the short-term results of preoperative chemoradiation therapy with S-1 for locally advanced rectal cancer. A total of 32 patients with advanced rectal cancer who had been treated with preoperative chemoradiotherapy with S-1 and underwent surgical resection between May 2012 and December 2019 were analyzed. Advanced rectal cancer of clinical stage II and III was diagnosed in 13 (41%) and 19 (59%) patients, respectively. Therapeutic toxicities of anemia (24 patients; 75%), anal pain (22 patients; 69%) and skin and subcutaneous tissue disorders (19 patients; 59%) were frequently observed in all grades. Grade ≥3 leukopenia, anemia, neutrophil count reduction, platelet count reduction and diarrhea were identified in 2 (6%), 1 (3%), 1 (3%), 1 (3%) and 1 (3%) patients, respectively. A total of 29 patients (91%) completed this therapy without any change to the protocol or dosage. R0 resection was performed in 100% of the patients, and no postoperative mortality was observed. Pathological complete response was observed in 9 cases (28.1%). This therapy can be considered for cases of locally advanced rectal cancer due to its acceptable toxicity and relatively high antitumor effect.

Baseline anaemia increases locally advanced rectal cancer mortality in older patients undergoing preoperative chemoradiation.

PURPOSE: The median diagnosis age of rectal cancer (RC) is 70 years old. The standard of care for locally advanced RC (LARC) is preoperative chemoradiation (CRT) followed by surgery. Anaemia is a frequent condition in older patients but is not a pure consequence of ageing. METHODS: The patients aged 65 years or over, with clinical stage II/III LARC, and treated with preoperative concurrent CRT were retrospectively reviewed. Baseline haemoglobin (Hb) levels were collected. RESULTS: One hundred and seven patients enrolled in this study, but 17 were excluded in relation with treatment disruption. Fifty-seven (63.3%) males and 33 (36.7%) females completed preoperative CRT whose median age at diagnosis was 73. Twenty-five (27.8%) patients presented with anaemia at rectal cancer diagnosis, and median Hb was 13.5 g/dL (IQR = 1.45) and 11.2 g/dL (IQR = 1.35), for non-anaemic and anaemic patients, respectively. For the enrolled older population, only 2 patients reported acute grade 3 toxicity. Baseline anaemia tended to decrease the LARC-free interval and was associated with a significantly higher hazard of all-cause and LARC mortality, approximately 5 times (HR = 5.25; 95% CI 1.48-18.66) and 10 times (HR = 10.09; 95% CI 2.40-42.48), respectively. Patients older than 75 presented a significantly negative impact on overall survival (OS) and LARC-specific survival (HR = 6.20, 95% CI 2.00-19.22; and HR = 7.61, 95% CI 2.08-27.87, respectively). Conversely, no significant impact was found for age-adjusted Charlson comorbidity index on OS, LARC-specific survival and LARC-free interval. CONCLUSIONS: Overall and LARC-specific survival were significantly lower for the baseline anaemic older patients and for those aged 75 years or over.

Clinical implications of the serum CA19-9 level in "biological borderline resectability" and "biological downstaging" in the setting of preoperative chemoradiation therapy for pancreatic cancer.

BACKGROUND: Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and "biological downstaging" in chemoradiation therapy (CRT) for pancreatic cancer (PC). METHODS: A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. "Biological downstaging" was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). RESULTS: The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). CONCLUSIONS: Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated "biological downstaging" in b-BR in the preoperative CRT strategy.

Oncological Outcomes After Radical Esophagectomy from a Tertiary Cancer Center.

Although esophageal cancers have poor survival outcomes, evidence suggests that preoperative chemoradiation followed by surgery have improved survival outcomes. Minimally invasive surgery has equivalent oncological outcomes with less complication compared with open surgery, but there is insufficient data available in South Indian population. Our aim was to analyze the perioperative outcome and survival between minimally invasive and open transhiatal esophagectomy group. Data from patients operated for esophageal cancer in our department from the year 2015 to 2018 were collected retrospectively using medical records. Among 55 carcinoma esophagus patients, squamous histology (67%) and lower third location (57%) being predominant. Twenty-six patients underwent video-assisted thoracoscopic surgery (VATS)-assisted esophagectomy and 18 patients underwent open transhiatal esophagectomy. Eleven patients were inoperable. Sixteen patients in VATS arm and three patients in transhiatal arm received preoperative chemoradiation. VATS arm has lesser intraoperative blood loss, early pulmonary recovery with early intercostal drain removal, and lesser hospital stay but longer mean operating time of 171 min versus 140 min (P < 0.01). It has higher mean nodal harvest of 15 versus 7 nodes (P 0.01) and higher overall median survival of 36 months (95% CI, 29.3 to 42.7) as against 23 months (95% CI, 17.8 to 29.2) for transhiatal arm (P < 0.01). VATS-assisted esophagectomy is less morbid procedure with early postoperative recovery, better oncological outcomes, and improved survival compared with transhiatal arm which is equivalent to apex centers in India.

Neoadjuvant strategies in resectable carcinoma esophagus: a meta-analysis of randomized trials.

BACKGROUND: The survival benefit of neoadjuvant therapy in resectable carcinoma esophagus has been elucidated. We performed a meta-analysis in light of new studies and long-term results of past trials. The search strategy was refined to include only "neoadjuvant" so that any bias by adjuvant treatment is eliminated. METHODS: A detailed search of MEDLINE, Embase, and Cochrane Library was done. Only published randomized English language trials were included. Data were categorized as neoadjuvant concurrent chemoradiation (NACRT), neoadjuvant chemotherapy (NACT), neoadjuvant radiotherapy (NART), and neoadjuvant sequential chemoradiotherapy (SCRT). Meta-analysis was done using odds ratio (OR) and 95% CI using fixed/random effects model. Heterogeneity was tested by chi-square and I2 test. Z probability calculated significant difference across subgroups. Outcomes assessed were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years, respectively, mortality (30/90 day) and failures (local/systemic). RESULTS: Twenty-five randomized trials involving 5272 patients were included for quantitative analysis. NACRT was evaluated in 12 studies (2676 patients). Superior 3-year OS (OR = 0.68 CI 0.52-0.90, p = 0.007), 3-year DFS (OR = 0.55 CI 0.45-0.68, p = 0.00001), and 5-year DFS (OR = 0.59 CI 0.47-0.74, p = 0.00001), with lower failures (OR = 0.52 CI 0.37-0.73, p = 0.0001), were seen in favor of NACRT at the cost of increased perioperative mortality (OR = 1.79 CI 1.15-2.80, p = .01). However, 5-year OS (OR = 0.78 CI 0.60-0.1.01, p = 0.06) was not found to be significantly superior. NACT, NART, and SCRT were not found to have any benefit over surgery alone. CONCLUSION: This meta-analysis presents strong evidence favoring NACRT over upfront surgery. It also shows no survival advantage of neoadjuvant chemotherapy.

The Anatomical Pattern of the Proximal Jejunal Vein as a Prognostic Factor in Patients With Pancreatic Head Cancer Treated With Preoperative Chemoradiation Therapy.

BACKGROUND/AIM: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC). PATIENTS AND METHODS: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed. RESULTS: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005). CONCLUSION: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival.

Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. METHODS: Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy. DISCUSSION: The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.

BACKGROUND: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. PATIENTS AND METHODS: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). RESULTS: Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. CONCLUSION: The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

How to Achieve a Higher Pathologic Complete Response in Patients With Locally Advanced Rectal Cancer Who Receive Preoperative Chemoradiation Therapy.

The current standard of care for treating patients with locally advanced rectal cancer includes preoperative chemoradiation therapy (PCRT) followed by a total mesorectal excision and postoperative adjuvant chemotherapy. A subset of these patients has achieved a pathologic complete response (pCR) and they have shown improved disease-free and overall survival compared to non-pCR patients. Thus, many efforts have been made to achieve a higher pCR through PCRT. In this review, results from various ongoing and recently completed clinical trials that are being or have been conducted with an aim to improve tumor response by modifying therapy will be discussed.