CLINICAL OUTCOME OF HIGH DOSE RADIOTHERAPY WITH OR WITHOUT CONCURRENT CHEMOTHERAPY IN ESOPHAGEAL CANCER (EC): A STUDY FROM NORTH – EAST INDIA

Objective:The objective of this study is comparision of local and distant control rates with high-dose versus standard-dose radiotherapy along with concurrent chemotherapy in esophageal cancer – a prospective randomized study.Materials and Methods:Histologically proven Stage I–III patients with carcinoma esophagus were randomized into two groups. One group has been treated with standard-dose radiotherapy, i.e., a total dose of 50.4 Gy (1.8 Gy/day, 28#, 5 days/week). The other group (study arm) has received high-dose radiotherapy, i.e. a total dose of 64.8 Gy (1.8 Gy/day, 36#, 5 days/week). Both groups have received 2 cycles of 3 weekly concurrent chemotherapy (cisplatin 75 mg/m[2] on day 1 and 5-fluorouracil 750 mg/m[2] continuous intravenous infusion over 24 h on day 1–4). Follow-up response evaluation was done by both endoscopy and computed tomography scan after 6–8 weeks and after 2 months thereafter.Results:Out of a total of 28 patients, 68% showed a complete response, 14% showed partial response, and 18% patients developed progressive disease at first and subsequent follow up (median follow-up of 21 months). Among the complete response patients, rates were higher in high-dose group compared to standard-dose radiotherapy group (71% vs. 64%, P = 0.38). Treatment-related toxicities were acceptable in both groups.Conclusion:High-dose radiotherapy with concurrent chemotherapy seems to be more effective with acceptable toxicity in our study. However, further follow-up and large sample size may be required to validate the current study conclusion.

Concurrent Chemotherapy and Proton Beam Therapy for Esophageal Cancer

Phase 2 Study of Intensity Modulated Radiation With Concurrent Chemotherapy as Definitive Treatment for Esophageal Squamous Cell Cancer

Objective To summarize the outcomes and prognostic factors in esophageal cancer(EC) patients treated with three-dimensional radiotherapy (3DCRT and IMRT) . Methods Five hundred ninety-two EC patients received three-dimensional radiotherapy (123 with 3DCRT, 469 with IMRT) in our hospital from January 2002 to March 2012. Three hundred and sixty patients received radiotherapy alone and 232 patients received radiotherapy and chemotherapy. The median radiotherapy dose was 60 Gy. Concurrent chemotherapy was used with paclitaxel plus platinum (weekly schedule). Sequential chemotherapy was used with paclitaxel or fluorouracil plus platinum (3-week schedule). The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS) , and the log-rank test was used for survival difference analysis and univariate prognostic analysis. The Cox regression model was used for multivariate prognostic analysis. Results The numbers of samples at 3 and 5 years were 142 and 53, respectively. The 1-year OS and PFS were 65.3%and 52.1%, respectively; the 3-year OS and PFS were 34.0% and 28.0%, respectively; the 5-year OS and PFS were 23.5% and 19.6%, respectively. The median OS was 20 months (95% CI:17.9-22.1 months) and the median PFS was 14 months (95% CI: 11.8-16.2 months). Univariate analysis indicated that sex, N stage, M stage, TNM stage, radiotherapy dose, weight loss before treatment, smoking, and drinking were prognostic factors for OS and PFS (P=0.002 and 0.000, 0.000 and 0.000, 0.001 and 0.000, 0.000 and 0.000, 0.000 and 0.000, 0.024 and 0.026, 0.009 and 0.005, 0.000 and 0.000). Multivariate analysis showed that TNM stage, radiotherapy dose, and sex were prognostic factors for OS and PFS (P=0.000 and 0.000,0.000 and 0.001,0.036 and 0.027) . Conclusions The outcomes of EC patients treated with three-dimensional radiotherapy alone or combined with chemotherapy are promising. Early TNM stage, high radiotherapy dose, and female sex are independently associated with better OS and PFS. Key words: Esophageal neoplasms/radiotherapy; Radiotherapy, three-dimensional conformal; Radiotherapy, intensity-modulated; Prognosis

Salvage Chemoradiation Therapy With Triple-Drug Combination (Docetaxel, 5-FU, and CDDP) for Postoperative Locoregional Recurrence pf Esophageal Cancer

Background: Esophageal cancer has a poor prognosis because most patients have locally advanced disease upon presentation, and are therefore not suitable for upfront surgery. Modern radiation therapy techniques using intensity modulated radiation therapy (IMRT) combined with a novel imaging technique using integrated positron emission tomography and computed tomography (PET/CT) may help radiation oncologists increase radiation dose to the tumor and may improve tumor response. Objective: The primary aim was to analyze the toxicity of dose-escalated IMRT using a simultaneous integrated boost (SIB) technique and concurrent chemotherapy in esophageal cancer patients using PET/CT as a guide for target delineation. Secondary endpoints were to evaluate response rate, overall survival, and event-free survival rates. Method: Seventeen consecutive patients with locally advanced carcinoma of the esophagus were treated with preoperative concurrent chemoradiation that consisted of IMRT 64 Gy in 30 fractions (SIB technique), together with two cycles of cisplatin (80 mg/m 2 , day 1 and 29) and 5-fluorouracil (1000 mg/m 2 /d, days 1–4 and 29–32). Baseline PET/CT was used for staging and target delineation. After complete chemoradiation for 3 months, PET/CT was repeated and the patients were evaluated for esophagectomy. Treatment toxicities were collected. Baseline and 3-month postchemoradiation PET/CT imaging were analyzed and correlated with the pathological findings. Result: The median follow-up time was 12 months. All 17 patients had squamous cell carcinoma of thoracic esophageal cancer and were treated with chemoradiation. The most common acute ≥grade 3 adverse effects were leucopenia (58.8) and vomiting (23.5%), respectively. Acute ≥grade 3 cardiotoxicities and pulmonary toxicities were observed in 5.9% and 11.7% of the patients, respectively. One patient (5.9%) died from an esophagopericardial fistula. Seven patients underwent esophagectomy after chemoradiation. A pathologic complete remission was achieved in 4 patients (57.1% of the surgical group or 23.5% of the entire group). The overall 1-year survival and event free survival rates for the entire group of patients were 87% and 59%, respectively. There was a statistically significant difference in the overall 1-year survival between surgical and nonsurgical groups (overall 1-year survival, 100% versus 74%, respectively, p = 0.037). In contrast, there was no significant difference in 1-year event-free survival between groups (1-year event-free survival, 72% versus 56%, p = 0.085). Applying the average absolute reduction and percentage reduction of SUV max in these patients, PET/ CT could not predict the pathologic response. Conclusion: Integrating PET/CT for dose-escalated IMRT in esophageal cancer patients showed acceptable toxicities and promising overall survival, especially when followed by surgery.

104 Background: In esophageal cancer (EC) patients not eligible for surgery definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard regime. Nowadays carboplatin and paclitaxel are also often used. In this study we compared survival and toxicity rates between both regimens. Methods: This multicentre study included 102 patients treated in five centres in the North Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU and 55 patients carboplatin/paclitaxel. Results: Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group (P=0.879, Hazard Ratio [HR] 0.97 confidence interval [CI] 0.62-1.51), with a median survival of respectively 16.1 (CI 11.8-20.5) and 13.8 (CI 10.8-16.9) months. Median disease free survival (DFS) was comparable (P=0.760, HR 0.93 CI 0.60-1.45) between the cisplatinum / 5-FU group (11.1 months, CI 6.9-15.3) and the carboplatin/paclitaxel group (9.7 months, CI 5.1-14.4). Groups were comparable except clinical T-stage was higher in the carboplatin/paclitaxel group (P=0.008), but a high clinical T-stage (cT4) was not related to OS and DFS in a univariate analysis (P=0.250 and P=0.201). A higher percentage of patients completed the carboplatin / paclitaxel regimen (82% compared to 57%, P=0.01). Hematological and non-hematological toxicity (≥ grade 3) was significantly lower in the carboplatin / paclitaxel group (4% and 18%) than in the cisplatinum/5-FU (19% and 38%, P=0.001). Conclusions: In this study we show comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared to cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with a higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment for cisplatinum/5-FU is a good candidate regimen for further evaluation.

Major research objectives

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.

Long-Term Outcome of Rectal Cancer Patients Treated by High-Dose Radiotherapy and Concurrent Chemotherapy

BACKGROUND AND OBJECTIVESWe aimed to evaluate long-term treatment outcomes and toxicity profile of combined radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer.DESIGN AND SETTINGSRetrospective study in a tertiary care cancer center in Riyadh, Saudi Arabia.METHODS AND MATERIALSThe medical records of patients with histopathologically proven, locally advanced cervical cancer were analyzed. These patients received three-dimensional conformal radiotherapy with concurrent chemotherapy followed by high dose rate brachytherapy in our center between July 2007 and April 2012. The data regarding the safety profile, response rates, occurrence of locoregional or distant failure, disease-free survival, and overall survival rates were recorded.RESULTSThe median follow-up period was 60 months (range, 8–66) for 74 patients. The median age of study population was 52.3 years (32–78), and the stage IIB was the predominant stage (49 patients [66.2%]). A total of 45 patients (60.9%) had radiologic-positive pelvic ± para-aortic lymphadenopathy. The 5-year locoregional and distant control rates were 84.3% and 78.5%, respectively. The 5-year disease-free and overall survival rates were 75.7% and 64.5%, respectively. Stage, nodal status, and hemoglobin levels were found to be important prognostic factors for locoregional and distant control. Acute grade 3 hematological and nonhematological toxicities were seen in 4 (5.4%) and 4 (5.4%) patients. Late toxicities were mild, and only 1 (1.4%) patient presented with subacute intestinal obstruction.CONCLUSIONConcurrent chemoradiation in Saudi women with locally advanced cervical cancer showed better locoregional and distant control and survival rates with minimal toxicity.

Background:Results of CheckMate 577 show an improved disease-free survival for patients with resected esophageal or gastroesophageal junction cancer treated with adjuvant nivolumab compared with placebo (22.4 versus 11.0 months). Population-based data can provide insights in outcomes from clinical practice. The aim of our study was to investigate disease-free and overall survival in a nationwide population aligned with the inclusion criteria of CheckMate 577.Patients and Methods:Resected patients with stage II/III esophageal or gastroesophageal junction cancer (2015–2016) treated with neoadjuvant chemoradiotherapy were selected from the Netherlands Cancer Registry. Patients with cervical esophageal cancer, irradical resection, or complete pathological response were excluded. Disease-free and overall survival were assessed from 12 weeks after resection using Kaplan-Meier methods. In addition, to adjust for differences in characteristics between CheckMate 577 and our population-based cohort, a matching-adjusted indirect comparison was performed for pathological lymph node status and pathological tumor status.Results:We identified 634 patients. Sixty percent of patients were diagnosed with recurrence or were deceased at the end of follow-up. Median disease-free survival was 19.7 months and median overall survival was 32.2 months. After the matching procedure, the median disease-free survival was 17.2 months and median overall survival was 28.2 months.Conclusions:Disease-free survival in our population-based study was considerably longer than the placebo population of CheckMate-577 (19.7 versus 11.0 months). Possible explanations are differences in characteristics, quality of esophageal cancer care, or differential strategies for evaluation of recurrence. In the Netherlands postoperative imaging is not part of the standard follow-up as opposed to the standard postoperative imaging in the CheckMate 577 trial. The difference in postoperative imaging could partially explain the longer disease-free survival observed in our study. Quality and optimization of current treatment modalities remain important aspects of esophageal cancer care.

BACKGROUNDThe global incidence of esophageal cancer (EC) remains high. Despite advancements in medical technology and deeper research into the causes and treatment methods of EC, the effectiveness of treatment for EC is still unsatisfactory. Therefore, it is crucial to address the urgent problem of improving the long-term survival rate of EC patients and providing personalized treatment.AIMTo analyze the survival prognosis and influencing factors of esophageal squamous cell carcinoma (ESCC).METHODSA retrospective analysis was conducted on the clinical data of 115 patients with pT3N0M0 ESCC who underwent radical surgery alone from January 1, 2013, to December 31, 2019. The Kaplan–Meier method was used to evaluate the 1-year, 3-year, and 5-year survival rates and median survival time of the patients. The Cox proportional hazards regression model was used to assess the hazard ratios (HRs) and 95% confidence intervals (95%CIs) of risk factors.RESULTSThe 1-year, 3-year, and 5-year overall survival (OS) rates for the 115 EC patients analyzed were 85.22%, 50.43%, and 37.48%, respectively. The median OS was 37.00 (95%CI: 24.93-49.07) months, and the median disease-free survival was 21.00 (95%CI: 14.71-27.29) months. Both univariate and multivariate Cox regression analyses revealed that high body mass index (BMI; HR = 1.137, 95%CI: 1.054-1.226), positive perineural invasion (PNI; HR = 13.381, 95%CI: 4.899-36.547), and smoking (HR = 2.415, 95%CI: 1.388-4.203) were independent risk factors for a poor prognosis. In contrast, compared to the upper thoracic location of the tumor, middle thoracic (HR = 0.441, 95%CI: 0.240-0.810) and lower thoracic (HR = 0.328, 95%CI: 0.144-0.750) locations were protective factors.CONCLUSIONBMI, tumor location, PNI, and smoking are associated with the prognosis of ESCC patients. This study highlights the prognostic risk factors for T3N0M0 ESCC patients and offers personalized insights for clinical treatment.

Factors Associated With Long-term Survival in Locally-Advanced Squamous Cell Carcinoma of the Vulva Treated With Definitive Radiation Therapy

Background:Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established.Methods:412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed.Results:Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3–122.0); 81.6 months (95% CI, 55.9–not estimable) for the DF group and 67.7 months (95% CI, 41.6–not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1–61.7) for the entire cohort; 49.5 months (95% CI, 38.6–70.3) for DF and 33.0 months (95% CI, 18.1–70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis.Conclusion:At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.