681 PATTERN OF RECURRENCE IN PATIENTS WITH A PATHOLOGICALLY COMPLETE RESPONSE AFTER NEOADJUVANT CHEMORADIOTHERAPY AND SURGERY FOR OESOPHAGEAL CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Marloes Jongh ◽  
Ben M Eyck ◽  
Leonie R Werf ◽  
Eelke L A Toxopeus ◽  
J Jan B Lanschot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Field ◽  
Oesophageal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Distant Recurrence ◽  
Time To Recurrence ◽  
Phase Ii And Iii ◽  
Pattern Of Recurrence

Abstract   Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20 and 50% of patients having a pathological complete response (pCR). Disease, however, still recurs in 20–30% of these patients. The aim of this study was to assess the pattern of recurrence in patients with pCR after nCRT and surgery. Methods All patients with pCR after neoadjuvant chemoradiotherapy and surgery included in the phase II and III ChemoRadiotherapy for Oesophageal followed by Surgery Study (CROSS) trials (April 2001—March 2009) and after the CROSS trials (September 2009—October 2017) were identified. The site of recurrence was compared to the applied radiation and surgical fields. Outcomes were median time to recurrence, overall and progression-free survivals. Results A total of 141 patients with a median follow-up of 100 (interquartile range [IQR] 64–134) months were included. Some 29 of 141 patients (21%) developed recurrence. Of these, four (14%) had isolated locoregional recurrence, 15 (52%) distant recurrence only and ten (34%) had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five were within the radiation field, seven outside the radiation field and two at the border. Median (IQR) time to recurrence was 24 (10–62) months. The 5-year overall survival was 74% and recurrence-free survival 70%. Conclusion Despite good overall survival, recurrence still occurred in 21% of patients. Most recurrences were distant, outside the radiation and surgical fields.

scholarly journals Pattern of recurrence in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer

BJS Open ◽  
2021 ◽  
Vol 5 (2) ◽  
Author(s):  
M de Jongh ◽  
B M Eyck ◽  
L R van der Werf ◽  
E L A Toxopeus ◽  
J J B van Lanschot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Radiation Field ◽  
Median Time ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Distant Recurrence ◽  
Free Survival ◽  
Time To Recurrence ◽  
Pattern Of Recurrence

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20–50 per cent of patients having a pathological complete response (pCR). Disease, however, still recurs in 20–30 per cent of these patients. The aim of this study was to assess the pattern of recurrence in patients with a pCR after nCRT and surgery. Methods All patients with a pCR after nCRT and surgery included in the phase II and III CROSS (ChemoRadiotherapy for Oesophageal followed by Surgery Study) trials (April 2001 to December 2008) and after the CROSS trials (September 2009 to October 2017) were identified. The site of recurrence was compared with the applied radiation and surgical fields. Outcomes were median time to recurrence, and overall and progression-free survival. Results A total of 141 patients with a median follow-up of 100 (i.q.r. 64–134) months were included. Some 29 of 141 patients (20,6 per cent) developed recurrence. Of these, four had isolated locoregional recurrence, 15 had distant recurrence only, and ten had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five had recurrence within the radiation field, seven outside the radiation field, and two at the border. Median time to recurrence was 24 (10–62) months. The 5-year overall survival rate was 74 per cent and the recurrence-free survival rate was 70 per cent. Conclusion Despite good overall survival, recurrence still occurred in 21 per cent of patients. Most recurrences were distant, outside the radiation and surgical fields.

272 10-YEAR FOLLOW-UP OF A RANDOMISED CONTROLLED TRIAL COMPARING NEOADJUVANT CHEMORADIOTHERAPY PLUS SURGERY VERSUS SURGERY ALONE FOR OESOPHAGEAL CANCER (CROSS)

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
B Eyck ◽  
J Lanschot ◽  
M Hulshof ◽  
B Wilk ◽  
J Shapiro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Oesophageal Cancer ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Oesophagogastric Junction ◽  
Randomised Controlled

Abstract   Neoadjuvant chemoradiotherapy according to the Dutch randomised controlled ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) has become standard of care for patients with cancer of the oesophagus or oesophagogastric junction. The aim of this study was to provide more insight into the ultra-long-term impact of CROSS neoadjuvant chemoradiotherapy on survival and disease recurrence for patients with oesophageal cancer. Methods Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction were randomised between neoadjuvant chemoradiotherapy (five weekly cycles of intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m2 of body-surface area]) with concurrent 41.4 Gy radiotherapy given in 23 fractions of 1.8 Gy, 5 days per week) plus surgery (nCRT arm) versus surgery alone (surgery arm). Primary endpoint was overall survival, defined from date of randomisation to date of all-cause death or to last day of follow-up. Secondary endpoints were cause-specific mortality and conditional survival. Analysis was by intention-to-treat. Results From 2004 through 2008, 178 patients were randomized to the nCRT arm and 188 to the surgery arm. Median follow-up for surviving patients was 146.6 months (IQR 133.5–157.2). Ten-year overall survival was 38% in the nCRT arm and 25% in the surgery arm (HR 0.68 [95%CI 0.53–0.87]). For patients with squamous cell carcinoma ten-year overall survival was 46% in the nCRT arm compared to 23% in the surgery arm. For patients with adenocarcinoma ten-year overall survival was 36% in the nCRT arm and 26% in the surgery arm. In the nCRT arm, ten-year oesophageal cancer-specific mortality was 47%. Conclusion Survival benefit of patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction receiving neoadjuvant chemoradiotherapy persists for at least 10 years compared to patients undergoing surgery alone.

scholarly journals Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ben M. Eyck ◽  
◽  
Berend J. van der Wilk ◽  
Bo Jan Noordman ◽  
Bas P. L. Wijnhoven ◽  
...  
Keyword(s):  
Overall Survival ◽  
Active Surveillance ◽  
Oesophageal Cancer ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Phase Iii ◽  
Residual Tumour ◽  
Trial Protocol ◽  
Stepped Wedge ◽  
Cluster Randomised

Abstract Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design The SANO trial protocol has been published (10.1186/s12885-018-4034-1). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.

Neoadjuvant chemotherapy followed by radical surgery in locally advanced vulvar carcinoma: a single-institution experience

2021 ◽  
pp. 030089162110276
Author(s):  
Adorni Marco ◽  
Bazzurini Luca ◽  
Lissoni Andrea Alberto ◽  
Vecchione Francesca ◽  
Negri Serena ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Vulvar Cancer ◽  
Elderly Women ◽  
Radical Surgery ◽  
Locally Advanced ◽  
Complete Response ◽  
Tumor Burden ◽  
Clinical Response Rate

Background: Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. Methods: Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. Results: Fourteen patients (93%) completed NACT with tolerable toxicities (G3–G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. Conclusion: NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.

651 A META-ANALYSIS OF SURVIVAL AFTER NEOADJUVANT CHEMORADIOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY IN RESECTABLE LOCALLY ADVANCED ESOPHAGEAL CANCERS BASED ON HISTOLOGIC SUBTYPES

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Rawat Waratchanont ◽  
Jirat Leelapatanadit ◽  
Wichitra Asanprakit ◽  
Viriya Kaewkangsadan ◽  
Sukchai Sattaporn
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Comprehensive Search ◽  
Complications And Mortality ◽  
Histologic Subtypes

Abstract   Neoadjuvant treatments provided survival benefits over surgery alone in resectable locally advanced esophageal and esophagogastric junction (EGJ) cancer patients. Both neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) are shown to be effective treatments. However, the direct comparison between two methods based on histologic subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC) is still limited. This study examined the hypothesis that nCRT could provide the better overall survival (OS) than nCT. Methods A comprehensive search of studies comparing nCRT and nCT in patients with esophageal and EGJ cancer based on histologic subtypes was conducted. A meta-analysis of randomized (8 articles) and non-randomized (15 articles) studies was performed using odds ratio (OR) and 95% confidence intervals (CI95%). The OS was the main objective, whereas the secondary objective were complete pathological response (pCR) rate, curative resection (R0) rate, locoregional progression free-survival (L-PFS) rate, postoperative complications and mortality. Results Twenty three articles included 1,671 SCC and 9,285 AC patients. Neither 3- nor 5-year OS was found to be different. However, SCC patients receiving nCRT showed the better 3-year OS (OR 1.67, CI95% 1.17–2.40, p = 0.005). Both pCR and R0 rates were superior in nCRT group (OR 3.30, CI95% 2.46–4.44 and 2.46, CI95% 1.66–3.65, p < 0.00001, respectively). The better 3-year L-PFS was observed in nCRT group (OR 1.47, CI95% 1.17–1.85, p = 0.008), but 5-year L-PFS was comparable. The 30-day mortality was comparable, while 90-day mortality was higher in nCRT group (OR 1.32, CI95% 1.01–1.72, p = 0.04). Conclusion The nCRT provided the better overall survival especially in SCC patients and also increased locoregional control. Meanwhile, postoperative complications and mortality were higher after nCRT. Due to clinical heterogeneity, the multidisciplinary team management for each patient is required before treatment.

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 231-231
Author(s):  
Lauren Jurkowski ◽  
Aditya Varnam Shreenivas ◽  
Sakti Chakrabarti ◽  
Mandana Kamgar ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Clinical Outcomes ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Metabolic Imaging ◽  
R0 Resection ◽  
Curative Intent

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.

796 OUTCOMES OF DELAYED SURGERY IN PATIENTS WITH RESIDUAL DISEASE AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR OESOPHAGEAL CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Hidde Overtoom ◽  
Ben Eyck ◽  
Berend Wilk ◽  
Bo Noordman ◽  
Pieter Sluis ◽  
...  
Keyword(s):  
Postoperative Complications ◽  
Oesophageal Cancer ◽  
Cox Regression ◽  
Residual Disease ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Tumour Regression ◽  
Tumour Regression Grade ◽  
Negative Effect

Abstract   Standard treatment for locally advanced oesophageal cancer is neoadjuvant chemoradiotherapy (nCRT), plus surgery 6-8 weeks later. Time to surgery (TTS) after nCRT seems safe up to 12 weeks, and possibly improves patient condition and pathological response. However, it is unknown whether prolonged TTS is safe in patients with residual disease. The aim of this study was to investigate whether prolonged TTS leads to inferior surgical outcomes and survival in patients with residual disease after nCRT. Methods Patients with pathologically confirmed residual disease 4-6 weeks after nCRT who underwent preoperative PET/CT and surgery were selected from the preSANO-trial and SANO-trial. Patients were stratified by TTS ≤12 weeks versus TTS >12 weeks after completion of nCRT. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), peroperative unresectability, microscopically radical resections (R0), tumour regression grade (TRG), postoperative complications and risk of distant dissemination. Effects of TTS on OS, PFS and distant dissemination were analysed with Cox regression, adjusted for Charlson comorbidity index (CCI) at baseline, as well as WHO performance score and weight loss after nCRT. Results Forty-two patients were included in the TTS >12 weeks and 132 patients in the TTS ≤12 weeks group. Median follow-up was 20.6 months (IQR 16.1-30.3). Adjusted hazard ratios for OS and PFS were 0.50 (95% CI: 0.24-1.02) and 0.47 (95% CI: 0.25-0.91), respectively, in favour of TTS >12 weeks. Patients with TTS >12 weeks had more postoperative complications (89% vs 72%, p = 0.049), but comparable peroperatively unresectable tumours (11.9% vs. 3.8%, p = 0.11), R0-resections (89% vs 87%, p = 0.89), and TRG-scores (p = 0.97) compared to patients with TTS ≤12 weeks. Patients with TTS >12 weeks showed less distant dissemination (HR 0.40, 95% CI: 0.18-0.88). Conclusion Prolonged TTS beyond 12 weeks in patients with clinically proven residual disease after nCRT did not have a negative effect on OS and on PFS, but was correlated with an increase in postoperative complications. The (non-significantly) better survival outcomes for TTS >12 weeks may be explained by the fact that patients had a lower risk of developing distant dissemination, which may reflect improved selection prior to surgery.

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