Abstract Background Response evaluation criteria in solid tumours (RECIST) are used to define degrees of response to anti-tumour agents. In retrospective analyses, early tumour shrinkage (ETS) has ...been investigated as an alternative early-on-treatment predictor of treatment efficacy with regard to progression-free and overall survival. While cut-off based analysis of ETS facilitates the categorisation of patients into responders and non-responders after a defined period of treatment, depth of response (DpR) serves as a continuous measure, which defines the nadir of tumour response. Methods A systematic literature search for ‘early tumour shrinkage’ or ‘tumour size decrease’ in ‘metastatic colorectal cancer’ reported from January 2000 to July 2014 was performed. The present review summarises available data concerning ETS and DpR and evaluates their potential as predictive markers for the clinical management of patients with metastatic colorectal cancer (mCRC). Results A total of 10 clinical trials investigated the role of ETS as a marker of clinical outcome in patients with mCRC. In addition, DpR was investigated using the efficacy data from three of these trials. Available data show that ETS differentiates patients with high sensitivity to treatment and more favourable prognosis from a heterogeneous group of patients classified as non-ETS patients. ETS is an early indicator of the potentially achievable response. In contrast, DpR estimates the nadir of tumour response as a continuous measure, which may affect the subsequent disease history, thus translating into superior survival. Conclusions The concepts of ETS and DpR offer potential as clinical end-points to aid the clinical decision making process and thus further optimise mCRC patient management in the era of tailored therapy approaches.
Primary tumor sidedness (left vs. right) has prognostic and predictive impact on anti-EGFR agent efficacy and thus management of metastatic colorectal cancer (mCRC). This analysis evaluates the ...relevance of primary tumor location (PTL) in
wild-type mCRC patients, when dividing the colorectal frame into six segments. This pooled analysis, performed on a single-patient basis of five randomized first-line therapy trials, evaluates the impact of exact PTL classification on baseline characteristics, prognosis and prediction of anti-EGFR antibody efficacy by chi-square and log-rank tests, the Kaplan-Meier method, Cox and logistic regressions. The PTL was significantly associated with metastatic spread: liver (
= 0.001), lung (
= 0.047), peritoneal (
< 0.001) and lymph nodes (
= 0.048). A multivariate analysis indicated an impact on anti-EGFR agent efficacy in terms of overall survival depending on the exact primary tumor location: from detrimental in caecal (HR 2.63), rather neutral effects in the ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99) and left flexure/descending colon (HR 0.91) to clear benefit in sigmoid (HR 0.71) and rectal (HR 0.58) primaries. Exact primary tumor location affects anti-EGFR antibody efficacy in a rather continuous than a dichotomous fashion in
wild-type mCRC patients. This perspective might help to support clinical decisions when anti-EGFR antibodies are considered.
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Background: Previous studies have shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various cancer entities in ...the metastatic setting, yet there is no evidence on the prognostic value of baseline HRQOL for patients undergoing radical cystectomy (RC) with curative intent. The goal of this study was to evaluate the influence of baseline preoperative HRQOL on cancer specific survival prognosis for patients undergoing RC. Methods: 407 patients with prospectively assessed baseline HRQOL prior RC were included. Patients were stratified by the global health status (GHS) domain of the EORTC QLQ-C30 questionnaire, and good general HRQOL was defined as GHS≥70 based on validated cut-off levels. A 1:2 propensity-score-matched analysis of n=357 patients n=125 (GHS≥70), n=232 (GHS<70) was performed. Primary endpoint was cancer-specific survival (CSS), secondary endpoints encompassed overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression models were performed to assess prognostic significance of baseline GHS on survival outcomes. Harrell’s discrimination C-index was assessed to calculate the predictive accuracy of the model (p<0.05). Results: Median follow-up was 40.5mo. Patients subcohorts were well-balanced. All baseline QLQ-C30 functioning scales were in favour of the GHS≥70 cohort (each p<0.001). 5-yr CSS (82% vs. 65%; p=0.001), 5-yr OS (76% vs 53%; p=0.001) and 5-yr-RFS (50% vs. 39%; p=0.04) and were significantly increased in the GHS≥70 cohort. GHS≥70 was confirmed as an independent predictor for increased CSS (HR 0.43, 95%CI 0.21–0.89; p=0.028), OS (HR 0.56, 95%CI 0.31–0.90; p=0.031) and RFS (HR 0.52, 95%CI 0.31–0.87; p=0.013) multivariate analysis. Conclusions: Our findings suggest preoperative baseline HRQOL to have a pronounced predictive value for patients undergoing RC with curative intent for bladder cancer. We found baseline good general HRQOL to accurately predict increased CSS, OS and RFS.Table: see text
The therapy of patients with colorectal liver metastases (CRLM) has undergone significant changes. Extended survival has been observed to be associated with adoption of hepatic resection and improved ...chemotherapy.
This review summarizes standards, developments and controversies on the management of these patients. Literature search was performed with focus on work published within the last ten years.
Patients with CRLM should undergo surgery whenever possible with careful and experienced patient selection as hepatic resection offers the best long-term prognosis. The multidisciplinary approach has markedly evolved and has increased the number of patients in whom curative-intended surgery is possible. Patients with resectable metastases can undergo upfront surgery or may receive perioperative chemotherapy in selected cases, a decision which is under debate and remains individual. Patients with non-resectable metastases that may become resectable upon conversion treatment should receive polychemotherapy with or without local ablative therapy as pretreatment with the main goal of achieving resectability. In patients with synchronous CRLM, the optimal sequence of treatment remains unclear. Depending on the hepatic tumor burden and its dynamics as well as the type and stage of the primary tumor, simultaneous resection or either the sequential "bowel-first" or reversed "liver-first" approach represent suitable options to achieve complete tumor clearance.
The improvements in the management of CRLM due to multidisciplinary treatment and novel developments are a great example of successfully pushing the boundaries of cure in metastatic cancer. Surgery aiming at complete tumor clearance represents the central instrument to achieve long-term survival.
Endometriosis is a common disorder in reproductive-age women leading to a broad range of symptoms and is associated with a higher risk for endometrioid ovarian carcinoma.
We report the case of a 55 ...year-old woman with previously undiagnosed endometriosis presenting with a large mediastinal cancer of unknown primary (CUP) and synchronous Union Internationale Contre le Cancer (UICC) stage II rectal adenocarcinoma. Histopathologically the mediastinal tumor resembled endometrial carcinoma and laparoscopically endometriotic lesions on the patient's peritoneum were detected. The patient was treated with neoadjuvant carboplatin and paclitaxel, followed by resection of the mediastinal tumor. After recovery, the patient received neoadjuvant short-course radiation to the rectal adenocarcinoma, which was resected afterwards. No primary endometrial carcinoma was found in the uterus, leading to the most likely conclusion that the mediastinal tumor derived from an extragenital endometriotic lesion.
Although rare, cases of degeneration of endometriosis have been described. In this case not only the localization of endometriosis was uncommon, but also its malignant transformation and synchronous diagnosis of a rectal adenocarcinoma, complicating diagnosis, and treatment of the patient. This rare case highlights the importance of diagnosing and treating patients with CUP or multiple malignancies at large interdisciplinary centers to reach the best possible outcome.
This study aimed to assess the consistency and replicability of treatment recommendations provided by ChatGPT 3.5 compared to gastrointestinal tumor cases presented at multidisciplinary tumor boards ...(MTBs). It also aimed to distinguish between general and case-specific responses and investigated the precision of ChatGPT's recommendations in replicating exact treatment plans, particularly regarding chemotherapy regimens and follow-up protocols.
A retrospective study was carried out on 115 cases of gastrointestinal malignancies, selected from 448 patients reviewed in MTB meetings. A senior resident fed patient data into ChatGPT 3.5 to produce treatment recommendations, which were then evaluated against the tumor board's decisions by senior oncology fellows.
Among the examined cases, ChatGPT 3.5 provided general information about the malignancy without considering individual patient characteristics in 19% of cases. However, only in 81% of cases, ChatGPT generated responses that were specific to the individual clinical scenarios. In the subset of case-specific responses, 83% of recommendations exhibited overall treatment strategy concordance between ChatGPT and MTB. However, the exact treatment concordance dropped to 65%, notably lower in recommending specific chemotherapy regimens. Cases recommended for surgery showed the highest concordance rates, while those involving chemotherapy recommendations faced challenges in precision.
ChatGPT 3.5 demonstrates potential in aligning conceptual approaches to treatment strategies with MTB guidelines. However, it falls short in accurately duplicating specific treatment plans, especially concerning chemotherapy regimens and follow-up procedures. Ethical concerns and challenges in achieving exact replication necessitate prudence when considering ChatGPT 3.5 for direct clinical decision-making in MTBs.
•ChatGPT 3.5 shows promise as a valuable tool in clinical decision-making.•ChatGPT 3.5 provides case-specific recommendations when provided with sufficient information.•In 83% of cases, ChatGPT 3.5 generates conceptual treatment recommendations that align with the MTB.•ChatGPT 3.5 struggles to generate case-specific recommendations, achieving a 65% concordance rate.
Amphiregulin (
) and epiregulin (
) are ligands of
. Predictive information for anti-
treatment in metastatic colorectal cancer (mCRC) was observed, but data for other agents is limited.
Ligand mRNA ...expression;
mutations; and
expression were assessed by qRT-PCR, pyrosequencing, and IHC, respectively, in mCRC tumor tissue of patients participating in the randomized controlled trials FIRE-1, CIOX, and FIRE-3. Normalized mRNA expression was dichotomized using median and third quartile. Overall (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method including univariate and multivariate Cox regression analyses. Penalized spline regression analysis tested interaction of mRNA expression and outcome.
Of 688 patients with available material, high
expression was detected in 343 (>median) and 172 (>3rd quartile) patients. High
expression was associated with significantly higher OS 26.2 vs. 21.5 months, HR = 0.80; 95% confidence interval (CI), 0.68-0.94;
= 0.007, PFS (10.0 vs. 8.1 months, HR = 0.74; 95% CI, 0.63-0.86;
= 0.001), and objective response rate (63.1% vs. 51.6%,
= 0.004) compared to low expression at both threshold values. This effect remained significant in multivariate Cox regression analysis (OS:
= 0.01, PFS:
= 0.002). High
mRNA expression interacted significantly with the efficacy of cetuximab compared with bevacizumab (OS:
= 0.02, PFS:
= 0.04) in
WT mCRC.
High
mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-
treatment.
Lynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and ...the cost-effectiveness of different testing strategies is unknown.
We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically.
On average, detected mutation carriers gained 0.52 life-years (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was euro 77,268, euro 253,258, and euro 4,188,036 per life-year gained, respectively.
The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.
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