Union Internationale Contre Le Cancer Research Articles

Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial.

IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab vs best supportive care (BSC) following platinum-based chemotherapy in the PD-L1-positive and all stage II-IIIA non-small cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are here reported. The design, participants, and primary-endpoint DFS outcomes have been reported for this phase 3, open-label, 1:1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) vs BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC. Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay). At a median 45.3 months' follow-up on April 18, 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified HR was 0.995 (95% CI 0.78-1.28). The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n=882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 TC ≥1% (n=476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n=229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis (grade 3/4 in 53 [10.7%] and grade 5 in 4 [0.8%] of 495 patients, respectively). Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.

Emergency resection is an independent risk factor for decreased long-term overall survival in colorectal cancer: a matched-pair analysis

BackgroundColorectal cancer is one of the most common malignant neoplasms worldwide. Up to 30% of the patients present in an emergency setting despite an established screening program. Emergency colorectal resection is associated with increased mortality and morbidity as well as worse oncological outcome. This study aims to analyze the impact on tumor recurrence and survival in patients with an emergency colorectal resection, independent of sex, age, and tumor stage.MethodsPatients, who underwent an oncological resection for colorectal cancer at the Medical University of Innsbruck, Department of Visceral, Transplant and Thoracic Surgery, between January 2003 and December 2018 were analyzed retrospectively and screened for emergency resections. Matched pairs were formed to analyze the impact of emergency operations on long-term outcomes, considering tumor stage, sex, and age, comparing it with elective patients.ResultsIn total, 4.5% out of 1297 patients underwent surgery in an emergency setting. These patients had higher UICC (Union internationale contre le cancer) stages than elective patients. After matching the patients for age, sex, and tumor stage, emergency patients still had higher mortality. The incidence of recurrence was higher (47.5% vs. 25.4%, p = 0.003) and the 5-year overall survival decreased (35.6% vs. 64.4%, p < 0.001) compared to the matched patients with elective resection. Correcting for 90-day mortality still a reduction in the 5-year overall survival was demonstrated (44% vs. 70%, p = 0,001). The left-sided colon tumors were more common in the emergency group (45.8% vs. 25.4%, p = 0.006) and the rectal tumors in the elective one (21.2% vs. 3.4%, p = 0.002).ConclusionPatients undergoing emergency resection for colorectal cancer have a decreased tumor-specific and overall survival compared to patients after elective resection, independent of age, sex, and tumor stage, even after correcting for 90-day mortality. These findings confirm the importance of colorectal cancer awareness and screening to reduce emergency resections.

Long-term oncological outcomes for minimally invasive surgery versus open surgery for colon cancer-a population-based nationwide study with a non-inferiority design.

The study aimed to compare 5-year overall survival in a national cohort of patients undergoing curative abdominal resection for colon cancer by minimally invasive surgery (MIS) or by the open (OPEN) technique. All patients diagnosed between 2010 and 2016 in Sweden with pathological Union International Contre le Cancer Stages I-III colon cancer localized in the caecum, ascending colon, hepatic flexure or sigmoid colon and those who underwent curative right sided hemicolectomy, sigmoid resection or high anterior resection by MIS or OPEN were included. Patients were identified in the Swedish Colorectal Cancer Registry from which all data were retrieved. The analyses were performed as intention-to-treat and the relationship between surgical technique (MIS or OPEN) and overall mortality within 5 years was analysed. For the primary research question a non-inferiority hypothesis was assumed with a statistical power of 90%, a one-side type I error of 2.5% and a non-inferiority margin of 2%. For the secondary analyses, multilevel survival regression models with the patients matched by propensity scores were employed, adjusted for patient- and tumour-related variables. A total of 11 605 pathological Union International Contre le Cancer Stages I-III patients were included with 3297 MIS (28.4%) and 8308 OPEN (71.6%) and were followed until 31 December 2020. The primary analysis demonstrated superiority for MIS compared to OPEN. The multilevel survival regression analyses confirmed that 5-year overall survival was higher in MIS with a hazard ratio of 0.874 (95% confidence interval 0.791-0.965), and if excluding pT4 the outcome was similar, with a hazard ratio of 0.847 (95% confidence interval 0.756-0.948). This observational study demonstrated that MIS was favourable to OPEN with regard to 5-year overall survival. These results support the use of laparoscopic colon cancer surgery in routine practice.

A Mass Spectrometry Imaging Based Approach for Prognosis Prediction in UICC Stage I/II Colon Cancer.

Simple SummaryTumor treatment is heavily dictated by the tumor progression status. However, in colon cancer, it is difficult to predict disease progression in the early stages. In this study, we have employed a proteomic analysis using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). MALDI-MSI is a technique that measures the molecular content of (tumor) tissue. We analyzed tumor samples of 276 patients. If the patients developed distant metastasis, they were considered to have a more aggressive tumor type than the patients that did not. In this comparative study, we have developed bioinformatics methods that can predict the tendency of tumor progression and advance a couple of molecules that could be used as prognostic markers of colon cancer. The prediction of tumor progression can help to choose a more adequate treatment for each individual patient.Currently, pathological evaluation of stage I/II colon cancer, following the Union Internationale Contre Le Cancer (UICC) guidelines, is insufficient to identify patients that would benefit from adjuvant treatment. In our study, we analyzed tissue samples from 276 patients with colon cancer utilizing mass spectrometry imaging. Two distinct approaches are herein presented for data processing and analysis. In one approach, four different machine learning algorithms were applied to predict the tendency to develop metastasis, which yielded accuracies over 90% for three of the models. In the other approach, 1007 m/z features were evaluated with regards to their prognostic capabilities, yielding two m/z features as promising prognostic markers. One feature was identified as a fragment from collagen (collagen 3A1), hinting that a higher collagen content within the tumor is associated with poorer outcomes. Identification of proteins that reflect changes in the tumor and its microenvironment could give a very much-needed prediction of a patient’s prognosis, and subsequently assist in the choice of a more adequate treatment.

Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial

Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients. IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours ≥4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II-IIIA population subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patients in the stage II-IIIA population, and finally the intention-to-treat (ITT) population (stage IB-IIIA). Safety was evaluated in all patients who were randomly assigned and received atezolizumab or best supportive care. IMpower010 is registered with ClinicalTrials.gov, NCT02486718 (active, not recruiting). Between Oct 7, 2015, and Sept 19, 2018, 1280 patients were enrolled after complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 in each group received treatment. After a median follow-up of 32·2 months (IQR 27·4-38·3) in the stage II-IIIA population, atezolizumab treatment improved disease-free survival compared with best supportive care in patients in the stage II-IIIA population whose tumours expressed PD-L1 on 1% or more of tumour cells (HR 0·66; 95% CI 0·50-0·88; p=0·0039) and in all patients in the stage II-IIIA population (0·79; 0·64-0·96; p=0·020). In the ITT population, HR for disease-free survival was 0·81 (0·67-0·99; p=0·040). Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11%) of 495 patients and grade 5 events in four patients (1%). IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II-IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC. F Hoffmann-La Roche and Genentech.

Reality of care of colorectal cancer in the State of Brandenburg : With special consideration of the number of hospital cases and certification as a colorectal cancer center

Analysis of the quality of care for colorectal cancer is an essential foundation for further development and is based on the comparison of the goals set and the actual quality of care. This publication presents the reality of care in the State of Brandenburg covering the complete spectrum of treating clinics based on the data of the clinical cancer register. This study analyzed the number of resected and examined lymph nodes, the quality of total mesorectal excision (TME), the residual tumor (R0) resection rate and the proportion of adjuvant therapy of colon cancer in Union internationale contre le cancer (UICC) stage III depending on the operation quota of hospitals and the certification as bowel cancer center according to Onkozert. Apart from the R status, the analyses showed no differences in the qualitative operation data from the clinical cancer register depending on the hospital volume.

Deep Learning Prediction of Metastasis in Locally Advanced Colon Cancer Using Binary Histologic Tumor Images.

Simple SummaryDeep learning methods are increasingly being applied for tissue classification to improve diagnosis and optimize therapy stratification. In this study, we developed the Binary ImaGe Colon Metastasis classifier (BIg-CoMet), a semi-guided approach for the stratification of colon cancer patients into two risk groups according to the occurrence of distant metastasis, using an InceptionResNetV2-based deep learning model trained on binary images. For a validation collective (n = 128), we showed that BIg-CoMet was able to stratify patients appropriately. The predicted high-risk group showed a worse clinical course for being metastasis-free, and the risk group was a prognostic factor for the occurrence of metastasis. These results were also found for both Union Internationale Contre le Cancer (UICC) subgroups. We demonstrated that Big-CoMet is useful for the stratification of colon cancer patients into risk groups based on images reflecting tumor architecture.In this study, we developed the Binary ImaGe Colon Metastasis classifier (BIg-CoMet), a semi-guided approach for the stratification of colon cancer patients into two risk groups for the occurrence of distant metastasis, using an InceptionResNetV2-based deep learning model trained on binary images. We enrolled 291 colon cancer patients with pT3 and pT4 adenocarcinomas and converted one cytokeratin-stained representative tumor section per case into a binary image. Image augmentation and dropout layers were incorporated to avoid overfitting. In a validation collective (n = 128), BIg-CoMet was able to discriminate well between patients with and without metastasis (AUC: 0.842, 95% CI: 0.774–0.911). Further, the Kaplan–Meier curves of the metastasis-free survival showed a highly significant worse clinical course for the high-risk group (log-rank test: p < 0.001), and we demonstrated superiority over other established risk factors. A multivariable Cox regression analysis adjusted for confounders supported the use of risk groups as a prognostic factor for the occurrence of metastasis (hazard ratio (HR): 5.4, 95% CI: 2.5–11.7, p < 0.001). BIg-CoMet achieved good performance for both UICC subgroups, especially for UICC III (n = 53), with a positive predictive value of 80%. Our study demonstrates the ability to stratify colon cancer patients via a semi-guided process on images that primarily reflect tumor architecture.

Notch Signaling Pathway in Pancreatobiliary Tumors.

Background and Objectives: The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival. Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas via immunohistochemistry and ImageJ software-assisted analysis. An Immunohistochemistry (IHC)-score was determined by the percentage and intensity of stained (positive) cells (scale 0–7) and normal and malignant tissue was compared. In the IHC results, patients’ (gender, age) and tumor (TNM Classification of Malignant Tumors, Union Internationale contre le Cancer (UICC) stages, grading, and lymphangitic carcinomatosa) characteristics were correlated to patient survival. Results: For eCC, the expression of CD44 (p = 0.043, IHC-score 3.94 vs. 3.54) and for iCC, the expression of CD44 (p = 0.026, IHC-score 4.04 vs. 3.48) and Notch1 (p < 0.001, IHC-score 2.87 vs. 1.78) was significantly higher in the tumor compared to non-malignant tissue. For PDAC, the expression of ADAM17 (p = 0.008, IHC-score 3.43 vs. 1.73), CD44 (p = 0.012, IHC-score 3.64 vs. 2.27), Notch1 (p = 0.012, IHC-score 2.21 vs. 0.64), and Notch4 (p = 0.008, IHC-score 2.86 vs. 0.91) was significantly higher in the tumor tissue. However, none of the analyzed Notch-signaling related components showed an association to patient survival. Conclusion: A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway’s relevance for patient survival.

Hybrid robotic versus hybrid laparoscopic Ivor Lewis oesophagectomy: a case-matched analysis

Robotic-assisted oesophagectomy for cancer has been increasingly employed worldwide; however, the benefits of this technique compared to conventional minimally invasive oesophagectomy are unclear. Since 2016, hybrid robotic minimally invasive oesophagectomy (R-HMIE) has increasingly replaced hybrid laparoscopic minimally invasive oesophagectomy (HMIE) as the standard of care in our institution. The aim of this study was to compare these procedures. Over a 10-year period, 686 patients underwent oesophagectomy at our institution. Out of these patients, 128 patients with cancer were treated with a hybrid minimally invasive technique. Each patient who underwent R-HMIE was matched according to gender, age, comorbidity, American Society of Anesthesiologists classification, Union International Contre le Cancer stage, localization, histology and neoadjuvant treatment with a patient who underwent HMIE. Perioperative parameters were extracted from our database and compared between the 2 groups. After the matching procedure, 88 patients were included in the study. Between HMIE and R-HMIE, no significant differences (P > 0.05) were found in operating time (median 281 vs 300 min), R0 resection rate (n = 42 vs 42), harvested lymph nodes (median 28 vs 24), hospital stay (median 19 vs 17 days) and intensive care unit stay (median 7 vs 6.5 days). Regarding surgical complications, no difference could be observed either (n = 42 vs 44). Minimally invasive oesophagectomy remains a challenging operation with high morbidity even in a high-volume institution. According to our intra- and short-term results, we have found no difference between R-HMIE and HMIE.

Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis.

Simple SummaryNon-small cell lung cancer (NSCLC) in stage III is often inoperable and highly heterogeneous. The primary gross tumor volume is prognostically relevant in several types of cancer, including oral carcinoma, B-cell lymphoma, and sarcoma. The planning target volume (PTV), including the primary tumor and involved lymph node stations, can vary widely, and its prognostic value for stage III is unclear. We aimed to evaluate the impact of the PTV for overall survival (OS), progression-free survival, and loco-regional control in 122 consecutive patients treated with definitive chemoradiotherapy (CRT). Median follow-up for the entire cohort was 41.2 (range: 4–108) months; median overall survival (OS) reached 20.9 (95% CI: 14.5–27.3) months. In a multivariate analysis including age, gender, total radiation dose, and histology, PTV ≥ 700 ccm was found to be an independent prognostic factor for OS (hazard ratio (HR): 1.705, 95% confidence interval (CI): 1.071–2.714, p = 0.025). In conclusion, non-operable stage III NSCLC patients with PTV ≥ 700 ccm showed significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC.Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and safety margins, can vary widely. In order to evaluate the impact of the PTV for overall survival (OS), progression-free survival (PFS) and loco-regional control, we analyzed retrospective and prospective data of 122 consecutive patients with inoperable stage III NSCLC treated with CRT. The majority of patients (93%) received a total dose ≥ 60 Gy and 92% of all patients were treated with concurrent or sequential chemotherapy. Median follow-up for the entire cohort was 41.2 (range: 3.7–108.4) months; median overall survival (OS) reached 20.9 (95% CI: 14.5–27.3) months. PTVs from 500 to 800 ccm were evaluated for their association with survival in a univariate analysis. In a multivariate analysis including age, gender, total radiation dose and histology, PTV ≥ 700 ccm remained a significant prognosticator of OS (HR: 1.705, 95% CI: 1.071–2.714, p = 0.025). After propensity score matching (PSM) analysis with exact matching for Union internationale contre le cancer (UICC) TNM Classification (7th ed.)T- and N-stage, patients with PTV < 700 ccm reached a median PFS and OS of 11.6 (95% CI: 7.3–15.9) and 34.5 (95% CI: 25.6–43.4) months vs. 6.2 (95% CI: 3.1–9.3) (p = 0.057) and 12.7 (95% CI: 8.5–16.9) (p < 0.001) months in patients with PTV ≥ 700 ccm, respectively. Inoperable stage III NSCLC patients with PTV ≥ 700 ccm had significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC.

The Effect of Resection Margin on Local Recurrence and Survival in High Grade Soft Tissue Sarcoma of the Extremities: How Far Is Far Enough?

Simple SummaryIn soft tissue sarcomas the width of surgical margins after resection determines the extent of surgery and the function after resection. But how far is really necessary? 305 patients with deep-seated, G2/3 soft tissue sarcomas of the extremity, the trunk wall, or the pelvis were reviewed. The 5-year local recurrence-free survival (LRFS) was 82%. Overall survival (OS) at 5 years was 66%. Positive (contaminated) margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. In conclusion the margin should at least be free of tumor, in sound tissue. A margin of >5 mm sound tissue seems to be sufficient. Resecting more tissue does not benefit the patient.Background: The significance of surgical margins after resection of soft tissue sarcomas in respect to local-recurrence-free survival and overall survival is evaluated. Methods: A total of 305 patients with deep-seated, G2/3 soft tissue sarcomas (STS) of the extremity, the trunk wall, or the pelvis were reviewed. The margin was defined according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification system (R0-2), the Union Internationale Contre le Cancer (UICC) classification (R + 1 mm) for which a margin <1 mm is included into the R1 group, and in groups of <1 mm, 1–5 mm, >5 mm, or >10 mm. Results: Of these patients, 31 (10.2%) had a contaminated margin, 64 (21%) a margin of <1 mm, 123 (40.3%) a margin of 1–5 mm, 47 (15.4%) a margin of >5 mm, and 40 (13.1%) a margin of >10 mm. The 5-year local recurrence-free survival (LRFS) was 81.6%. Overall survival (OS) at 5 years was 65.9%. Positive margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. Conclusions: A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. This finding supports use of the UICC classification. A margin of more than 10 mm did not improve LRFS or OS.

Comparison of Postoperative Acute Kidney Injury Between Laparoscopic and Laparotomy Procedures in Elderly Patients Undergoing Colorectal Surgery.

Postoperative acute kidney injury (AKI) has an unfavorable impact on both short-term and long-term outcomes. The aim of this retrospective study was to compare the incidence of postoperative AKI between laparoscopic and laparotomy procedures in elderly patients undergoing colorectal surgery. Medical records of elderly (65 y and older) patients who underwent colorectal cancer surgery between May 2016 and July 2018 at our tertiary hospital were reviewed. Patients with Union Internationale Contre le Cancer (UICC) stage II and III colorectal cancer, without neoadjuvant treatment, were divided into laparoscopic procedure group and laparotomy group. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups, before and after propensity matching. Multivariable analysis was made to identify independent risk factors of AKI. In all, 285 patients met the study inclusion criteria. Postoperative AKI occurred only in 16 patients from the laparotomy group (n=212). The incidence of AKI was significantly lower in the laparoscopic procedure group (n=73) compared with the laparotomy group (0% vs. 7.5%; P=0.015). Seventy-three patients who underwent laparoscopic surgery were matched with 73 of 212 patients who underwent open surgery, by using propensity score analysis, and the incidence of AKI in the 2 groups was similar (0% vs. 8.3%; P=0.028). Multivariable analysis showed that intraoperative metaraminol dose >1 mg (odds ratio=2.742, P=0.042) is an independent risk factor for postoperative AKI. In elderly patients, the incidence of AKI after colorectal cancer surgery is lower in the laparoscopic procedure group, maybe related to hemodynamic stability and less vasoconstriction.

Targeted and Checkpoint Inhibitor Therapy of Metastatic Malignant Melanoma in Germany, 2000-2016.

Targeted therapies (TT) and immune checkpoint inhibitors (ICI) have become increasingly important in the treatment of metastatic malignant melanoma in recent years. We examined implementation and effectiveness of these new therapies over time in Germany with a focus on regional differences. We analyzed data from 12 clinical cancer registries in 8 federal states in Germany over the period 2000–2016. A total of 3871 patients with malignant melanoma in Union internationale contre le cancer (UICC) stage IV at primary diagnosis (synchronous metastases) or with metachronous metastases were included. We investigated differences in survival of patients treated with new and conventional therapies by log-rank tests for Kaplan–Meier curves. Cox regression models were estimated to adjust therapy effects for demographic, regional, and prognostic factors. New systemic therapies were increasingly applied throughout Germany. TT were most frequently documented in Eastern Germany (East: 11.2%; West: 6.3%), whereas ICI therapies were more frequently used in Western Germany (East: 1.7%; West: 3.9%). TT had a relevant influence on patient survival (hazard ratio (HR) = 0.831; 95%-CI = (0.729; 0.948)). Survival was worse in Eastern Germany (HR = 1.470; 95%-CI = (1.347; 1.604)) relative to Western Germany. Treatment and survival prospects of patients with melanoma differed considerably between Western and Eastern Germany. The differences in regional medication behavior and survival require further exploration.

Correlations of UICC tumor stage and tumor regression on T2-weighted MRI sequences during definitive radiotherapy of cervical cancer.

The purpose of this study is to detect a correlation between the preradiation tumor staging and the relative volumetric regression of the primary tumor through external beam radiation therapy (EBRT). Clinical data of 32 patients with a mean age of 60±12 years treated with primary radiation therapy (RT) of cervical carcinoma were analyzed. Union Internationale Contre le Cancer (UICC) stages were T1 = 4 patients, T2 = 15 patients, T3 = 8 patients, T4 = 5 patients; N1 = 26 patients, N0 = 6 patients; and M0 = 25 patients, M1 = 7 patients. All patients received pelvic magnetic resonance imaging (MRI) before RT as well as during RT. The cervical primary tumor was delineated as gross tumor volume (ptGTV) in T2-weighted MRI sequences. We compared ptGTV reduction by stage, lymph node status, metastatic status, and grading. Mean ptGTV reduction during RT was 61.4±28.9%. T1 tumors shrank by 88.2±13.4%, T2 by 67.6±28.7%, T3 by 50.8±23.6%, and T4 by 38.7±27.2%. The difference in tumor shrinkage was statistically significant between the lower T stages and the higher T stages (p < 0.05). There was no statistical difference in the mean ptGTV before treatment in the group with lymph node metastases (LNM) (54.1±47.7 cm3) as compared to the group without LNM (76.6±52.2 cm3). Nonetheless, ptGTV shrank significantly differently: by 68.9±25.7% (N1 patients) and by 29.0±17.7% (N0 patients). No significant differences in ptGTV shrinkage were observed in M0 versus M1 and G2 versus G3 tumors. There is a correlation between mean ptGTV reduction during EBRT and tumor stages. Tumors with higher T stages shrank less under radiation treatment, and the ptGTV of N1 patients responded better than that of N0 patients.

Reporting and handling of lymphonodectomy specimens in gynecologic malignancies and sentinel lymph nodes

Die Aufarbeitung von Lymphonodektomiepräparaten gynäkologischer Malignome orientiert sich an den nationalen AWMF-Leitlinien und internationalen Empfehlungen. Die Definition von Mikrometastasen und isolierten Tumorzellen entspricht den Festlegungen der UICC(Union Internationale Contre le Cancer)/TNM(TNM-Klassifikation maligner Tumoren). Deren Nachweis soll im Befundbericht erwähnt werden sowie in die Tumorklassifikation einfließen. Alle übersandten Lymphknoten (LK) sollen untersucht werden mit vollständiger Einbettung aller LK bis 0,3 cm und Lamellierung aller größeren Lymphknoten parallel zu ihrer kurzen Achse in ca. 0,2 cm dicken Scheiben. Bestandteile des histologischen Befundberichtes sind: Zahl der befallenen LK im Verhältnis zur Zahl der entfernten/untersuchten LK entsprechend der Entnahmelokalisationen, metrische Ausdehnung der größten LK-Metastase, Fehlen/Nachweis einer extrakapsulären Ausbreitung. Zuschnitt und Einbettung von Sentinel-LK mit oder ohne Schnellschnittuntersuchung erfolgt in Analogie zu Nicht-Sentinel-LK mit Anfertigung von ca. 3 HE-gefärbten Stufenschnitten in einem Abstand von ca. 200 µm sowohl vom Gefrier- als auch Paraffinblock. Stellen sich die Sentinel-LK in der HE-Färbung negativ dar, soll ein immunhistochemisches Ultrastaging erfolgen.

Short-term and long-term outcomes of oesophagogastric surgery for cancer in obese and normal weight patients.

Obesity is generally considered to be associated with worse surgical outcome and impaired oncological prognosis. The impact of pre-therapeutic body mass index (BMI) in patients with oesophagogastric cancer on the surgical outcome is controversially discussed. We retrospectively examined 730 patients who had undergone curative treatment for oesophagogastric cancer at the Medical Center of the University of Freiburg (1996-2015). Patients were divided in groups according to pre-therapeutic BMI (underweight (UW): <18.5 kg/m2 ; normal weight (NW): 18.5-25 kg/m2 ; overweight (OW): 25-30 kg/m2 ; and obese (OB): >30 kg/m2 ). Median BMI was 24.7 kg/m2 . Forty-two patients were UW, 337 NW, 263 OW and 84 OB. No significant differences between the groups (UW/NW/OW/OB) in operating time, hospital stay, perioperative complication rate and in-hospital mortality were found. Pre-therapeutic BMI was significantly associated with 5-year survival (UW: 22%, NW: 37%, OW: 51%, OB: 50%, P < 0.001). Multivariate analysis identified UW/NW (BMI <25 kg/m2 ) as an independent risk factor for poor survival (relative risk 1.38, P = 0.001) among high American Society of Anesthesiologists score, old age, positive resection margin and high cancer stage according to the Union Internationale Contre le Cancer (UICC). In oesophagogastric cancer, OW and OB patients can be treated surgically without impaired perioperative outcome and expect improved long-term survival compared to patients with a BMI <25 kg/m2 .

Low VDAC1 Expression Is Associated with an Aggressive Phenotype and Reduced Overall Patient Survival in Cholangiocellular Carcinoma.

Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor periphery, all OXPHOS complexes were reduced except complex I. In addition, significantly lower levels of complex IV were found at the tumor center (p < 0.0001). Mitochondrial mass, as indicated by VDAC1 expression, was significantly increased in CCCs compared to corresponding normal tissue (p < 0.0001). VDAC1 levels were inversely correlated with UICC (Union Internationale Contre le Cancer) cancer stage classification (p = 0.0065). Furthermore, significantly lower VDAC1 was present in patients with lymph node involvement (p = 0.02). Consistent with this, patients whose carcinomas expressed VDAC1 at low to moderate levels had significantly reduced survival compared to high expressors (p < 0.05). Therefore, low mitochondrial mass is associated with more aggressive CCC. These metabolic features are indicative of a Warburg phenotype in CCCs. This metabolic signature has potential therapeutic implications because tumors with low mitochondrial function may be targeted by metabolic therapies such as a high-fat, low-carbohydrate ketogenic diet.

Colorectal cancer stage at diagnosis in migrants and non-migrants: across-sectional analysis of the KoMigra Study in Germany.

Colorectal cancer is one leading cause of cancer-related morbidity and mortality. Its prognosis depends largely on tumour stage at diagnosis. Migration status was associated with late stage at diagnosis in some studies, yet results are inconsistent. The cross-sectional study "The Diagnostics of Colorectal Carcinoma in Migrants and Non-Migrants in Germany" (KoMigra) investigated the association between migration background and tumour stage of colorectal cancer at diagnosis in a large German urban area. Patient variables were collected via a survey translated into nine languages. Data on tumour stage were extracted from medical records. 437 patients could be recruited for analysis. Explorative logistic regression yielded no significant difference for tumour stage "I" versus "II-IV" according to the tumour classification "Union Internationale Contre le Cancer" (UICC) between migrants and non-migrants. Although the odds of a higher tumour stage were consistently higher in migrants than non-migrants, the effect estimates had wide confidence intervals. In descriptive analyses, migrants reported symptoms more often and for longer time than non-migrants. This was especially true for patients with poor proficiency of German. Migration background was not significantly associated with advanced tumour stage at diagnosis. However, the effect of poor language proficiency should be explored further.

Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.

Clinicopathological Stratification and Long-term Follow-up of Patients with Periampullary Carcinomas.

Periampullary carcinomas generally confer a poor outcome. Choosing the most effective treatment regimen for each sub-entity proves challenging and is usually based on experience from pancreatic adenocarcinoma (PDAC). The long-term follow-up is presented of 472 patients with periampullary tumors [PDAC, distal cholangiocarcinoma (dCC) and ampullary carcinomas (AC)] who underwent radical resection considering clinical characteristics, paraclinical findings and histopathological features in order to define factors of prognostic relevance. Patients with PDACs presented with larger tumor sizes, more frequent R1 resection, higher rate of nodal and perineural invasion, higher tumor stage according to the classification of tumors of the Union Internationale contre le Cancer when compared to those with dCCs and ACs. In a multivariate analysis, age >65 years, postoperative complications and higher grading of the tumor proved to be independent prognostic factors for survival. Patients suffering from PDAC have the worst prognosis and greatest benefit from radical resection of all patients with periampullary tumors. More detailed studies are warranted to better distinguish between the different entities.