Does the ypTNM-stage adequately predict long-term survival rates in gastric cancer patients receiving neoadjuvant chemotherapy followed by radical resection?

BACKGROUND: Following neoadjuvant chemotherapy (NAC) for resectable gastric cancer, the prognostic adequacy of the UICC staging system needs to be investigated. In particular to explore whether the ypTNM curves for radically resected gastric cancer patients receiving NAC follow the stage-matched survival curves of radically resected chemo-naïve patients (pTNM). Further, to disclose any interaction between the TNM-response mode to NAC and stage-specific survival rates, i.e., whether survival for a particular pathological disease stage was dependent on whether this was reached through a downstaging or as stable disease following NAC. MATERIAL AND METHODS: Retrospective study on radically resected patients ≤ 75 years of age with gastric adenocarcinoma stages I-III diagnosed during 2001-2016. The patients constitute two population-based cohorts; the SURG-group with n = 121 patients treated before 2007 when NAC was introduced, and the NAC-group with n = 126 patients diagnosed since early 2007, receiving NAC and subsequent radical resection. RESULTS: Long-term survival rates were similar when specific ypTNM-stages were compared to their corresponding pTNM chemo-naïve counterparts. The dichotomised N0 vs. N + had a substantial impact on the long-term survival rates in both groups, however, no discrepancy in long-term survival rates between pN0 vs. ypN0, and pN + vs. ypN + was found. The pathological stage determined long-term survival rates irrespective of the baseline disease stage, as no interaction between the response mode and stage-specific survival rates was found. CONCLUSIONS: Survival curves for specific ypTNM-stages following NAC did not differ from the corresponding survival curves of their chemo-naïve pTNM counterparts. The interpretation is that NAC affected the gastric cancer, lymph nodes, and micrometastases, in such a way that the final ypTNM-stage provided similar prognostic information as the chemo-naïve pTNM-stages. Survival rates were contingent on the final ypTNM-stages alone, and not influenced by the response mode to reach that particular disease stage, or predetermined by the original clinical TNM-stage.

Response Evaluation after Neoadjuvant Chemotherapy for Resectable Gastric Cancer.

BACKGROUND: The method of response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer has been widely debated. An essential prerequisite is the ability to stratify patients into subsets of different long-term survival rates based on the response mode. Histopathological measures of regression have their limitations, and interest resides in CT-based methods that can be used in everyday settings. METHODS: We conducted a population-based study (2007-2016) on 171 consecutive patients with gastric adenocarcinoma who were receiving NAC. Two methods of response evaluation were investigated: a strict radiological procedure using RECIST (downsizing), and a composite radiological/pathological procedure comparing the initial radiological TNM stage to the pathological ypTNM stage (downstaging). Clinicopathological variables that could predict the response were searched for, and correlations between the response mode and long-term survival rates were assessed. RESULTS: RECIST failed to identify half of the patients progressing to metastatic disease, and it was unable to assign patients to subsets with different long-term survival rates based on the response mode. However, the TNM stage response mode did achieve this objective. Following re-staging, 48% (78/164) were downstaged, 15% (25/164) had an unchanged stage, and 37% (61/164) were upstaged. A total of 9% (15/164) showed a histopathological complete response. The 5-year overall survival rate was 65.3% (95% CI 54.7-75.9%) for TNM downstaged cases, 40.0% (95% CI 20.8-59.2%) for stable disease, and 14.8% (95% CI 6.0-23.6%) for patients with TNM progression, p < 0.001. In a multivariable ordinal regression model, the Lauren classification and tumor site were the only significant determinants of the response mode. CONCLUSIONS: Downsizing, as a method for evaluating the response to NAC in gastric cancer, is discouraged. TNM re-staging by comparing the baseline radiological CT stage to the pathological stage following NAC is suggested as a useful method that may be used in everyday situations.

The value of restaging CT following neoadjuvant chemotherapy for resectable gastric cancer. A population-based study.

BACKGROUND: Response evaluation following neoadjuvant chemotherapy (NAC) in gastric cancer is debated. The aim of this study was to investigate the value of UICC-downstaging as mode of response evaluation following a MAGIC-style regimen of NAC. METHODS: Retrospective, population-based study on consecutive patients with resectable gastric adenocarcinoma receiving NAC from 2007 to 2016. CT-scan was obtained at diagnosis (rTNM) and repeated following NAC (yrTNM) to evaluate response in terms of downstaging. Further, yrTNM stage was crosstabulated to pathologic stage (ypTNM) to depict correlation between radiologic and pathologic assessment. RESULTS: Of 171 patients receiving NAC, 169 were available for response evaluation. For TNM-stages, 43% responded, 50% had stable disease and 7% progressed at CT. Crosstabulating yrTNM stage to ypTNM stage, 24% had concordant stages, with CT overstaging 38% and understaging 38% of the tumours, Cohen kappa ƙ = 0,06 (95%CI 0.004-0.12). Similar patterns of discordance were found for T-stages and N-stages separately. For M-category, restaging CT detected 12 patients with carcinomatosis, with an additional 14 diagnosed with carcinomatosis only at operation. No patient developed parenchymal or extra abdominal metastases, and none developed locally non-resectable tumour during delivery of NAC. Restaging CT with response evaluation was not able to stratify patients into groups of different long-term survival rates based on response mode. CONCLUSIONS: Routine CT-scan following NAC is of limited value. Accuracy of CT staging compared to final pathologic stage is poor, and radiologic downstaging as measure of response evaluation is unreliable and unable to discriminate long-term survival rates based on response mode.

[Routines for first prescription of oral contraceptives]. / Rutiner ved førstegangsforskrivning av p-piller.

BACKGROUND: There is an increasing awareness about the risk of thromboembolic disease caused by combination oral contraceptives. This study assesses routines associated with prescription of an oral contraceptive, with an emphasis on venous thromboembolic disease. MATERIAL AND METHODS: A questionnaire requesting information about medical history, examinations, and general routines when an oral contraceptive was prescribed for the first time was sent to general practitioners, public health nurses and midwives in two Norwegian counties in 2008. A slightly different questionnaire was distributed to a group of female medical students. They were requested to describe the queries, procedures and information they were subjected to when oral contraceptives was first prescribed for themselves. RESULTS: In total, 99-100% of the prescribers reported that they asked about smoking habits and venous thromboembolic disease in the family. 94% of the doctors and 100% of the public health nurses/midwives informed about the risk of venous thromboembolic disease (p=0.028). The students reported that they had been asked, examined and informed less often than that reported by health professionals. 54% of the physicians and 11% of the public health nurses /midwives most often prescribed third generation oral contraceptives (p < 0.001). INTERPRETATION: Doctors, midwives and public health nurses seem to examine and inform their patients thoroughly about the risk of venous thromboembolic complications when prescribing combination oral contraceptives for the first time. Public health nurses and midwives seem to have a more rational prescription pattern of combined oral contraceptives than doctors.