Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.

OBJECTIVE: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer. SUMMARY BACKGROUND DATA: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity. METHODS: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT. RESULTS: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups. CONCLUSION: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis.

OBJECTIVE: Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS: Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS: For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION: The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer.

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24-71) (8/17), specificity of 85% (95% CI 42-99) (6/7), positive predictive value (PPV) of 89% (95% CI 51-99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17-67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6-51) (3/14), specificity of 100% (95% CI 56-100) (7/7), PPV of 100% (95% CI 31-100) (3/3), and NPV of 39% (95% CI 18-64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Fractures and other chest wall abnormalities after thoracotomy for esophageal cancer: A retrospective cohort study.

BACKGROUND: Chest pain following a thoracotomy for esophageal cancer is frequently reported but poorly understood. This study aimed to (1) determine the prevalence of thoracotomy-related thoracic fractures on postoperative imaging and (2) compare complications, long-term pain, and quality of life in patients with versus without these fractures. METHODS: This retrospective cohort study enrolled patients with esophageal cancer who underwent a thoracotomy between 2010 and 2020 with pre- and postoperative CTs (<1 and/or >6 months). Disease-free patients were invited for questionnaires on pain and quality of life. RESULTS: Of a total of 366 patients, thoracotomy-related rib fractures were seen in 144 (39%) and thoracic transverse process fractures in 4 (2%) patients. Patients with thoracic fractures more often developed complications (89% vs. 74%, p = 0.002), especially pneumonia (51% vs. 39%, p = 0.032). Questionnaires were completed by 77 after a median of 41 (P25 -P75 28-91) months. Long-term pain was frequently (63%) reported but was not associated with thoracic fractures (p = 0.637), and neither were quality of life scores. CONCLUSIONS: Thoracic fractures are prevalent in patients following a thoracotomy for esophageal cancer. These thoracic fractures were associated with an increased risk of postoperative complications, especially pneumonia, but an association with long-term pain or reduced quality of life was not confirmed.

Characteristics Predicting Short-Term and Long-Term Health-Related Quality of Life in Patients with Esophageal Cancer After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Esophagectomy is associated with lasting effect on health-related quality of life (HRQOL). Patients desire detailed information on the expected impact of treatment on their postoperative HRQOL. The aim of the present study is to identify clinicopathological characteristics predictive for changes in short-term and long-term HRQOL after neoadjuvant chemoradiotherapy (nCRT) and surgery. METHODS: HRQOL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior to nCRT, three, six, nine and twelve months postoperatively and at a minimum of six years postoperatively. Based on previous experience and available literature, several subgroups were predefined for different clinicopathological characteristics: baseline global HRQOL, WHO performance status, histology, tumor stage and tumor location. The primary endpoints of the present study were the change compared to baseline in the HRQOL dimensions physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. RESULTS: In total, 134 (76%) of 177 patients who received HRQOL questionnaires, responded at baseline. Patients who reported a high baseline global HRQOL had a more severe deterioration in eating problems (+14.5 to + 18.0), global HRQOL (-16.0 to -28.0) and fatigue (+10.5 to +14.9) up to six years postoperatively compared to patients who reported a low baseline global HRQOL. Patients who had stage 2 tumor (UICC 6th edition) had a more severe deterioration in eating problems (+14.6 to +19.0) and global HRQOL (-10.1 to -17.1) than patients who had stage 3 tumor. CONCLUSIONS: The results suggest that patients with locally advanced esophageal cancer in favorable condition at baseline decline more in terms of various HRQOL outcomes.

Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy: dysphagia is uncommon.

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.

Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer: A Systematic Review and Individual Patient Data Meta-analysis.

OBJECTIVE: To compare overall survival of patients with a cCR undergoing active surveillance versus standard esophagectomy. SUMMARY OF BACKGROUND DATA: One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy. METHODS: A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression-free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO: CRD42020167070). RESULTS: Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 [95% confidence interval (CI): 0.62-1.87, P = 0.75] after intention-to-treat analysis and 0.93 (95% CI: 0.56-1.54, P = 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95% CI: 0.83-1.58, P = 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95% CI: 26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection. CONCLUSIONS: Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic follow-up is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.

Outcomes after totally minimally invasive versus hybrid and open Ivor Lewis oesophagectomy: results from the International Esodata Study Group.

BACKGROUND: Large studies comparing totally minimally invasive oesophagectomy (TMIE) with laparoscopically assisted (hybrid) oesophagectomy are lacking. Although randomized trials have compared TMIE invasive with open oesophagectomy, daily clinical practice does not always resemble the results reported in such trials. The aim of the present study was to compare complications after totally minimally invasive, hybrid and open Ivor Lewis oesophagectomy in patients with oesophageal cancer. METHODS: The study was performed using data from the International Esodata Study Group registered between February 2015 and December 2019. The primary outcome was pneumonia, and secondary outcomes included the incidence and severity of anastomotic leakage, (major) complications, duration of hospital stay, escalation of care, and 90-day mortality. Data were analysed using multivariable multilevel models. RESULTS: Some 8640 patients were included between 2015 and 2019. Patients undergoing TMIE had a lower incidence of pneumonia than those having hybrid (10.9 versus 16.3 per cent; odds ratio (OR) 0.56, 95 per cent c.i. 0.40 to 0.80) or open (10.9 versus 17.4 per cent; OR 0.60, 0.42 to 0.84) oesophagectomy, and had a shorter hospital stay (median 10 (i.q.r. 8-16) days versus 14 (11-19) days (P = 0.041) and 11 (9-16) days (P = 0.027) respectively). The rate of anastomotic leakage was higher after TMIE than hybrid (15.1 versus 10.7 per cent; OR 1.47, 1.01 to 2.13) or open (15.1 versus 7.3 per cent; OR 1.73, 1.26 to 2.38) procedures. CONCLUSION: Compared with hybrid and open Ivor Lewis oesophagectomy, TMIE resulted in a lower pneumonia rate, a shorter duration of hospital stay, but higher anastomotic leakage rates. Therefore, no clear advantage was seen for either TMIE, hybrid or open Ivor Lewis oesophagectomy when performed in daily clinical practice.

Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: multicentre East Asian and Dutch database comparison.

BACKGROUND: Patients with different ethnic and genetic backgrounds may respond differently to anticancer therapies. This study aimed to assess whether patients with oesophageal squamous cell carcinoma (OSCC) treated with neoadjuvant chemoradiotherapy (nCRT) in East Asia had an inferior pathological response compared with patients treated in Northwest Europe. METHODS: Patients with OSCC who underwent nCRT according to the CROSS regimen (carboplatin and paclitaxel with concurrent 41.4 Gy radiotherapy) followed by oesophagectomy between June 2012 and April 2020 were identified from East Asian and Dutch databases. The primary outcome was pCR, defined as ypT0 N0. Groups were compared using propensity score matching, adjusting for sex, Charlson Co-morbidity Index score, tumour location, cT and cN categories, interval between nCRT and surgery, and number of resected lymph nodes. RESULTS: Of 725 patients identified, 133 remained in each group after matching. A pCR was achieved in 37 patients (27.8 per cent) in the Asian database and 58 (43.6 per cent) in the Dutch database (P = 0.010). The rate of ypT1-4 was higher in Asian than Dutch data (66.2 and 49.6 per cent; P = 0.004). The ypN1-3 rate was 44.4 per cent in the Asian and 33.1 per cent in the Dutch data set. Clear margins were achieved in 92.5 per cent of Asian and 95.5 per cent of Dutch patients. CONCLUSION: Regional differences in responses to CROSS nCRT for oesophageal cancer were apparent, the origin of which will need evaluation.

Bite-on-bite biopsies for the detection of residual esophageal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Active surveillance after neoadjuvant treatment is increasingly implemented. The success of this strategy relies on the accurate detection of residual cancer. This study aimed to assess the diagnostic value of a second (bite-on-bite) biopsy for the detection of residual esophageal cancer and to correlate outcomes to the distribution of residual cancer found in the resection specimen. METHODS: A multicenter prospective study of esophageal cancer patients undergoing active surveillance after neoadjuvant chemoradiotherapy was performed. At clinical response evaluations, an upper gastrointestinal (GI) endoscopy was performed with at least four bite-on-bite biopsies of the primary tumor site. First and second biopsies were analyzed separately. Patients with histopathological evidence of residual cancer were included in the primary analysis. Two pathologists blinded for biopsy outcome examined all resection specimens. RESULTS: Between October 2017 and July 2020, 626 upper GI endoscopies were performed in 367 patients. Of 138 patients with residual cancer, 112 patients (81 %) had at least one positive biopsy. In 14 patients (10 %) only the first biopsy was positive and in 25 patients (18 %) only the second biopsy (P = 0.11). Remarkably, the rates of patients with tumor-free mucosa and deeper located tumors were higher in patients detected by the first biopsy. The second biopsy increased the false-positive rate by 3 percentage points. No adverse events occurred. CONCLUSIONS: A second (bite-on-bite) biopsy improves the detection of residual esophageal cancer by almost 20 percentage points, at the expense of increasing the false-positive rate by 3 percentage points. The higher detection rate is explained by the higher number of biopsies obtained rather than by the penetration depth.

Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. SUMMARY OF BACKGROUND DATA: After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified. METHODS: Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses. RESULTS: Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma. CONCLUSIONS: Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study.

BACKGROUND: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. METHODS: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. DISCUSSION: If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). TRIAL REGISTRATION: The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).

The Rainbow Scale for the Assessment of the Cervicomental Angle: A Validated Scale.

BACKGROUND: Aging of the neck results in an increased cervicomental angle, which can be treated by various surgical and nonsurgical procedures. To measure the success of these procedures, standardized validated objective photographic measurement tools are needed. However, no online standardized photographic measurement tools exist for the assessment of the cervicomental angle. OBJECTIVES: The purpose of this study was to establish a validated and reliable measurement tool for the assessment of the cervicomental angle based on the Rainbow Scale. METHODS: A 5-point photographic rating scale was developed and created from 1 photograph with Adobe Photoshop. Fifteen reference photographs of women, 3 photographs per grade, were included for validation. Seven panelists (ie, plastic and maxillofacial surgeons) assessed the reference photographs 3 times with a minimal interval of 3 days in an online survey. Intra- and inter-observer agreements were calculated utilizing the weighted kappa coefficient. RESULTS: Mean intra-observer agreement was 0.93 (0.78-1.00). Mean interobserver agreement was 0.796 (0.574-0.961) for survey 1, 0.868 (0.690-0.960) for survey 2, and 0.820 (0.676-0.959) for survey 3. CONCLUSIONS: The Rainbow Scale for the assessment of the cervicomental angle has been validated in an online fashion. The scale is reproducible and reliable and requires no learning curve. Potential applications include objective assessment of neck treatment planning and surgical outcome.

Towards an Organ-Sparing Approach for Locally Advanced Esophageal Cancer.

BACKGROUND: Active surveillance after neoadjuvant therapies has emerged among several malignancies. During active surveillance, frequent assessments are performed to detect residual disease and surgery is only reserved for those patients in whom residual disease is proven or highly suspected without distant metastases. After neoadjuvant chemoradiotherapy (nCRT), nearly one-third of esophageal cancer patients achieve a pathologically complete response (pCR). Both patients that achieve a pCR and patients that harbor subclinical disseminated disease after nCRT could benefit from an active surveillance strategy. SUMMARY: Esophagectomy is still the cornerstone of treatment in patients with esophageal cancer. Non-surgical treatment via definitive chemoradiotherapy (dCRT) is currently reserved only for patients not eligible for esophagectomy. Since salvage esophagectomy after dCRT (50-60 Gy) results in increased complications, morbidity and mortality compared to surgery after nCRT (41.4 Gy), the latter seems preferable in the setting of active surveillance. Clinical response evaluations can detect substantial (i.e., tumor regression grade [TRG] 3-4) tumors after nCRT with a sensitivity of 90%, minimizing the risk of development of non-resectable recurrences. Current scarce and retrospective literature suggests that active surveillance following nCRT might not jeopardize overall survival and postponed surgery could be performed safely. Key Message: Before an active surveillance approach could be considered standard treatment, results of phase III randomized trials should be awaited.

The Rainbow Scale for Assessing Breast Ptosis: Validation of Three Different Views.

BACKGROUND: Photographic scales have become an increasingly used tool in objectively assessing outcomes in aesthetic surgery. However, no online photographic scale for assessing breast ptosis has been developed yet that is readily available. OBJECTIVES: This study was designed to validate the online Rainbow Scale for the assessment of breast ptosis for the anterior-posterior (AP), lateral, and oblique views. METHODS: For the five grades of the Rainbow Scale format, standardized reference photographs were selected. Six plastic surgeons rated 15 photographs for each view three times. Intra- and inter-observer agreements were calculated by using the weighted kappa coefficient and differences in intra- and inter-observer agreements between the three views were assessed for statistical significance using the Kruskal-Wallis test. RESULTS: The mean intra-observer agreements were 0.91 (range, 0.82-0.98) for the AP view, 0.88 (range, 0.77-1.00) for the oblique view, and 0.86 (range, 0.74-0.97) for the lateral view and did not vary significantly between all three views. The mean inter-observer agreements were 0.88 (range, 0.77-0.95) for the AP view, 0.84 (range, 0.72-0.94) for the oblique view, and 0.82 (range, 0.58-0.95) for the lateral view. The mean inter-observer agreements of the AP view varied significantly from the oblique view (P = .012) and the lateral view (P = .001). CONCLUSIONS: The Rainbow Scale for breast ptosis has been validated for the AP view, the lateral view, and the oblique view and is reproducible and reliable for the assessment of breast ptosis in three different views in an online setup. LEVEL OF EVIDENCE: 4 Diagnostic.

Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality. Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet-ring cells, and/or poorly cohesive cells.

Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts.

Chemotherapy aNd chemoradiotherapy for adenocarcinoma of the OESophagus and esophagogastric junction with oligometastases: Protocol of the TNT-OES-1 trial.

Background: FLOT and CROSS are effective neoadjuvant regimens for esophageal cancer patients. Chemotherapy (FLOT) is aimed to have merely a systemic effect whereas neoadjuvant chemoradiotherapy (CROSS) achieves good locoregional response with clinically complete response (cCR) rates up to 33% [1]. The aim of the present study is to assess safety and feasibility of dual therapy (FLOT-CROSS) in patients with oligometastases. Methods: This phase-II single-center, single-arm, intervention study includes patients with oligometastatic adenocarcinoma of the esophagus or esophagogastric junction. Patients will be treated with four biweekly cycles of FLOT, consisting of intravenous fluorouracil (2600 mg/m2), leucovorin (200 mg/m2), oxaliplatin (85 mg/m2) and docetaxel (50 mg/m2). Response evaluation by CT-scan will be performed 4-6 weeks after completion of FLOT. In case of regression or stable disease according to RECIST criteria (v.1.1), patients will receive additional CROSS, consisting of five weekly cycles of intravenous carboplatin (AUC 2) and paclitaxel (50 mg/m2), with concurrent 41.4 Gy radiotherapy, in 23 daily fractions of 1.8 Gy [2]. Response evaluation by endoscopy with biopsies, endoscopic ultrasonography and CT-scan will be performed 4-6 weeks after completion of CROSS. Primary endpoint is tolerability of FLOT-CROSS, defined as the proportion of patients who complete the full regimen. Secondary endpoints include disease control rate, objective response rate, overall survival and progression-free survival. In total, 20 patients will be included. Discussion: If patients are able to complete and tolerate FLOT-CROSS, this regimen should be tested in a phase-III trial and as neoadjuvant treatment in patients with locally advanced non-metastatic esophageal or junctional adenocarcinoma.