This study assessed the associations between hospital volume, resection rate and survival of oesophageal and gastric cancer patients in England.
62,811 patients diagnosed with oesophageal or gastric ...cancer between 2004 and 2008 were identified from a national population-based cancer registration and Hospital Episode Statistics-linked dataset. Cox regression analyses were used to assess all-cause mortality according to hospital volume and resection rate, adjusting for case-mix variables (sex, age, socioeconomic deprivation, comorbidity and type of cancer). HRs and 95% CIs, according to hospital volume, were evaluated for three predefined periods following surgery: <30, 30-365, and >365 days. Analysis of mortality in relation to resection rate was performed among all patients and among the 13 189 (21%) resected patients.
Increasing hospital volume was associated with lower mortality (p trend=0.0001; HR 0.87, 95% CI 0.79 to 0.95 for hospitals resecting 80+ and compared with <20 patients a year). In relative terms, the association between increasing hospital volume and lower mortality was particularly strong in the first 30 days following surgery (p trend<0.0001; HR 0.52, (0.39 to 0.70)), but a clinically relevant association remained beyond 1 year (p trend=0.0011; HR 0.82, (0.72 to 0.95)). Increasing resection rates were associated with lower mortality among all patients (p trend<0.0001; HR 0.86, (0.84 to 0.89) for the highest, compared with the lowest resection quintile).
With evidence of lower short-term and longer-term mortality for patients resected in high-volume hospitals, this study supports further centralisation of oesophageal and gastric cancer surgical services in England.
Tumour-associated fat cells without desmoplastic stroma reaction at the invasion front (Stroma AReactive Invasion Front Areas (SARIFA)) is a prognostic biomarker in gastric and colon cancer. The ...clinical utility of the SARIFA status in oesophagogastric cancer patients treated with perioperative chemotherapy is currently unknown.
The SARIFA status was determined in tissue sections from patients recruited into the MAGIC (n = 292) or ST03 (n = 693) trials treated with surgery alone (S, MAGIC) or perioperative chemotherapy (MAGIC, ST03). The relationship between SARIFA status, clinicopathological factors, overall survival (OS) and treatment was analysed.
The SARIFA status was positive in 42% MAGIC trial S patients, 28% MAGIC and 48% ST03 patients after pre-operative chemotherapy. SARIFA status was related to OS in MAGIC trial S patients and was an independent prognostic biomarker in ST03 trial patients (HR 1.974, 95% CI 1.555-2.507, p < 0.001). ST03 patients with lymph node metastasis (ypN + ) and SARIFA-positive tumours had poorer OS than patients with ypN+ and SARIFA-negative tumours (p
< 0.001).
The SARIFA status has clinical utility as prognostic biomarker in oesophagogastric cancer patients irrespective of treatment modality. Whilst underlying biological mechanisms warrant further investigation, the SARIFA status might be used to identify new drug targets, potentially enabling repurposing of existing drugs targeting lipid metabolism.
Response to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and ...validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides.
In this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA). We trained a deep learning-based classifier to detect microsatellite instability and EBV positivity from digitised, haematoxylin and eosin stained resection slides without annotating tumour containing regions. The performance of the classifier was assessed by within-cohort cross-validation in all ten cohorts and by external validation, for which we split the cohorts into a five-cohort training dataset and a five-cohort test dataset. We measured the area under the receiver operating curve (AUROC) for detection of microsatellite instability and EBV status. Microsatellite instability and EBV status were determined to be detectable if the lower bound of the 95% CI for the AUROC was above 0·5.
Across the ten cohorts, our analysis included 2823 patients with known microsatellite instability status and 2685 patients with known EBV status. In the within-cohort cross-validation, the deep learning-based classifier could detect microsatellite instability status in nine of ten cohorts, with AUROCs ranging from 0·597 (95% CI 0·522–0·737) to 0·836 (0·795–0·880) and EBV status in five of eight cohorts, with AUROCs ranging from 0·819 (0·752–0·841) to 0·897 (0·513–0·966). Training a classifier on the pooled training dataset and testing it on the five remaining cohorts resulted in high classification performance with AUROCs ranging from 0·723 (95% CI 0·676–0·794) to 0·863 (0·747–0·969) for detection of microsatellite instability and from 0·672 (0·403–0·989) to 0·859 (0·823–0·919) for detection of EBV status.
Classifiers became increasingly robust when trained on pooled cohorts. After prospective validation, this deep learning-based tissue classification system could be used as an inexpensive predictive biomarker for immunotherapy in gastric cancer.
German Cancer Aid and German Federal Ministry of Health.
Esophageal and gastric cancer have a poor prognosis and surgical intervention is associated with considerable morbidity, highlighting the need for careful preoperative assessment. The Incremental ...Shuttle Walk Test (ISWT) and Cardiopulmonary exercise testing (CPET) can assess preoperative fitness. This study aims to investigate their correlation with both postoperative respiratory complications and overall survival.
Patients were identified who underwent esophageal or gastric resections for cancer between 2010 and 2014 and had ISWT and/or CPET assessments. Tumor differentiation, stage, postoperative respiratory complications, and outcome were documented and then correlated with the results of the preoperative fitness assessments.
Neither the ISWT result, anaerobic threshold (AT) nor VO2 Max correlated well with perioperative complications. However, ISWT (p < 0.001), AT (p < 0.001) and VO2 Max (p < 0.001) all correlated strongly with overall survival. No patient with a score of less than 350 m on ISWT survived beyond 3 years. In a subset of patients with ISWT results both pre and post chemotherapy (n = 49), those that had an improvement in result had a 19% incidence of post-operative respiratory complications compared to 45% where the result did not change or declined, though due to small numbers this only approached significance (p = 0.08).
ISWT and CPET can be useful preoperative tools to predict overall survival for patients undergoing esophago-gastric resection. Furthermore, patients that improve their functional status during chemotherapy seem to do better than those where it remains static or declines.
To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients.
...Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC. Follicular hyperplasia in LNneg is associated with better survival in cancer-bearing mice and might explain increased LN size.
The long axis of 304 LNnegs was measured in hematoxylin-eosin stained sections from resection specimens of 367 OE02 trial patients (188 treated with surgery alone (S), 179 with neoadjuvant chemotherapy plus surgery (C+S)) as a surrogate of LN size. The relationship between LNneg size, LNneg microarchitecture, clinicopathological variables, and OS was analyzed.
Large LNneg size was related to lower pN category ( P = 0.01) and lower frequency of lymphatic invasion ( P = 0.02) in S patients only. Irrespective of treatment, (y)pN0 patients with large LNneg had the best OS. (y)pN1 patients had the poorest OS irrespective of LNneg size ( P < 0.001). Large LNneg contained less lymphocytes ( P = 0.02) and had a higher germinal centers/lymphocyte ratio ( P = 0.05).
This is the first study to investigate LNneg size in EC patients randomized to neoadjuvant chemotherapy followed by surgery or surgery alone. Our pilot study suggests that LNneg size is a surrogate marker of the host antitumor immune response and a potentially clinically useful new prognostic biomarker for (y)pN0 EC patients. Future studies need to confirm our results and explore underlying biological mechanisms.
Background
The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruption to global healthcare delivery. In England, the majority of elective surgery was postponed or cancelled to ...increase intensive care capacity. Our unit instituted the ‘RM Partners Cancer Hub’ at the Royal Marsden Hospital in London, to deliver ongoing cancer surgery in a ‘COVID-lite’ setting. This article describes the operational set-up and outcomes for upper gastrointestinal (UGI) cancer resections performed during this period.
Methods
From April 2020 to April 2021, the Royal Marsden Hospital formed the RM Partners Cancer Hub. This approach was designed to coordinate resources and provide as much oncological treatment as feasible for patients across the RM Partners West London Cancer Alliance. A UGI surgical case prioritisation strategy, along with strict infection control pathways and pre-operative screening protocols, was adopted.
Results
A total of 231 patients underwent surgery for confirmed or suspected UGI cancer during the RM Partners Cancer Hub, with 213 completed resections and combined 90-day mortality rate of 3.5%. Good short-term survival outcomes were demonstrated with 2-year disease free survival (DFS) and overall survival (OS) for oesophageal (70.8% and 72.9%), gastric (66.7% and 83.3%) and pancreatic cancer resections (68.0% and 88.0%). One patient who developed perioperative COVID-19 during the RM Partners Cancer Hub operation made a full recovery with no lasting clinical sequelae.
Conclusion
Our experience demonstrates that the RM Partners Cancer Hub approach is a safe strategy for continuing upper gastrointestinal (GI) resectional surgery during future periods of healthcare service disruption
There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is ...lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma.
Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index.
In total, 17,930 LNs from 763 patients were examined. LN response classified as
(LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%),
(LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%),
(LNRS 4-5; n = 303, 39.7%), or
(no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio HR, 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%).
Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.
Background
The optimal treatment strategy for elderly patients with gastric cancer is still controversial. This study aimed to assess the impact of age on short- and long-term outcomes after ...treatment for primary gastric cancer.
Methods
From January 2004 to December 2014, a total of 507 patients underwent gastrectomy for gastric adenocarcinoma at two high-volume upper gastrointestinal (GI) centers. The patients were classified into three groups as follows: group A (patients ≤ 69 years old,
n
= 266), group B (patients 70–79 years old,
n
= 166), and group C (patients ≥ 80 years old,
n
= 75). Clinicopathologic characteristics as well as, short- and long-term outcomes were compared between the groups.
Results
The patients in groups B and C had more comorbidities, whereas the younger subjects (group A) had more advanced tumor stages. Less extensive surgery was performed in the groups B and C. Older patients (age ≥ 70 years) had more postoperative medical complications. Moreover, group C had a higher postoperative mortality rate (8.1%) than group A (1.8%) or group B (1.9%). In the multivariable analysis, age older than 80 years (group C) was a negative independent factor for overall survival (OS) (hazard ratio HR, 2.36) compared with group A, whereas group B seemed to have a comparable risk (HR, 1.37). Notably, the three groups did not show significant differences in disease-related survival (DRS).
Conclusion
The data suggest that patients 70–79 years of age show a risk of postoperative death comparable with that of younger subjects. However, patients older than 80 years should be carefully selected for surgical treatment due to the increased risk of postoperative mortality.
Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus ...capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates.
Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas’ Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells.
Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50–0.94) and disease-free survival (HR = 0.75, 95% CI 0.58–0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups.
Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable.
•Better survival in patients treated with fluorouracil plus leucovorin, oxaliplatin and docetaxel.•Better pathological and radiological response to chemotherapy with FLOT.•Higher rates of complete pathological response in patients treated with FLOT.•Patients treated with FLOT were less likely to have a positive resection margin.•Comparable rates of surgical complications, adverse events and chemo completion.
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