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Importance: Patients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment are at high risk of developing locoregional and distant metastasis, yet optimal postsurgical treatment of these patients is limited., Objective: To analyze the association of PLNM with pretreatment clinical parameters, intensity of neoadjuvant treatment, and long-term oncological outcomes., Design, Setting, and Participants: This cohort study is a post-hoc analysis of 3 randomized clinical trials (Surgical Oncology Working Group of Germany [CAO], Radiological Oncology Working Group of Germany [ARO], and Working Group for Internal Oncology in the German Cancer Society [AIO]) conducted in Germany in 1994, 2004, and 2012 that included 1948 patients with locally advanced rectal cancer recruited between February 1995 and January 2018. Statistical analysis was conducted between September 2023 and February 2024., Exposures: Receiving preoperative fluorouracil-based chemoradiotherapy (CRT, comprising the preoperative group of CAO/ARO/AIO-94 and the control group of CAO/ARO/AIO-04), fluorouracil-based CRT plus oxaliplatin (experimental group of CAO/ARO/AIO-04), or total neoadjuvant treatment (TNT) with fluorouracil-based CRT plus oxaliplatin with induction or consolidation leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin chemotherapy within the CAO/ARO/AIO-12 trial., Main Outcome and Measures: The associations of PLNM with clinical parameters, intensity of neoadjuvant treatment, and cumulative incidences of LR, DM, and overall survival were assessed., Results: A total of 1888 patients (1333 male participants [70.6%]; median [range] age, 62 [19-84] years) with locally advanced rectal adenocarcinoma (clinical tumor stage 3 to 4 and/or clinically node-positive) treated within 3 consecutive clinical trials were analyzed. A total of 522 (29%) experienced PLNM; 378 had lymph node stage (ypN) 1 (20%) after neoadjuvant treatment (ypN) 1 (20%), and 174 had ypN2 (9%). Age, clinical T-stage, N-stage, grading, carcinoembryonic antigen levels, and time interval from completion of CRT to surgery were significantly associated with PLNM, whereas sex and tumor location were not. The percentage of patients with ypN2 stage was almost halved after TNT (18 of 293 patients [6%]) compared with patients treated with fluorouracil-based CRT (114 of 1009 patients [11.3%]; χ26 = 16.693; P = .01). After a median (IQR) follow-up of 54 (37-62) months, 5-year overall survival was 86.1% (95% CI, 83.9%-88.4%) for ypN0, 74.0% (95% CI, 83.9%-88.4%) for ypN1, and 43% for ypN2 (95% CI, 35.4%-52.2%) (P < .001). The 5-year cumulative incidences of locoregional and distant metastases were, respectively, 3% (95% CI, 2.1%-4.2%) and 20% (95% CI, 18%-23%) for ypN0, 6% (95% CI, 3.4%-8.8%) and 40% (95% CI, 34%-46%) for ypN1, and 19% (95% CI, 13%-26%) and 72% (95% CI, 63%-79%) for ypN2 (both P < .001)., Conclusions and Relevance: In this cohort study, PLNM unmasked an unfavorable phenotype of rectal cancer at high risk for treatment failure. More aggressive adjuvant treatment might be considered; however, risk-adapted surveillance strategies and early recurrence-directed surgery, if feasible, are important strategies in this group of patients with CRT- and/or chemotherapy-resistant disease.

In the context of the COVID-19 pandemic, there has been a scarcity of resources with various effects on the care of cancer patients. This paper provides an English summary of a German guideline on prioritization and resource allocation for colorectal and pancreatic cancer in the context of the pandemic. Based on a selective literature review as well as empirical and ethical analyses, the research team of the CancerCOVID Consortium drafted recommendations for prioritizing diagnostic and treatment measures for both entities. The final version of the guideline received consent from the executive boards of nine societies of the Association of Scientific Medical Societies in Germany (AWMF), 20 further professional organizations and 22 other experts from various disciplines as well as patient representatives. The guiding principle for the prioritization of decisions is the minimization of harm. Prioritization decisions to fulfill this overall goal should be guided by (1) the urgency relevant to avoid or reduce harm, (2) the likelihood of success of the diagnostic or therapeutic measure advised, and (3) the availability of alternative treatment options. In the event of a relevant risk of harm as a result of prioritization, these decisions should be made by means of a team approach. Gender, age, disability, ethnicity, origin, and other social characteristics, such as social or insurance status, as well as the vehemence of a patient's treatment request and SARS-CoV-2 vaccination status should not be used as prioritization criteria. The guideline provides concrete recommendations for (1) diagnostic procedures, (2) surgical procedures for cancer, and (3) systemic treatment and radiotherapy in patients with colorectal or pancreatic cancer within the context of the German healthcare system., (© 2024 S. Karger AG, Basel.)

Importance: Oncologic outcomes among patients with rectal cancer after developing local recurrence and/or distant metastases remain poorly studied., Objective: To analyze the trend of overall survival after treatment failure for patients with rectal cancer within three consecutive phase 2 or 3 trials of the German Rectal Cancer Study Group., Design, Setting, and Participants: This cohort study is a post hoc analysis of 3 randomized phase 2 or 3 trials (CAO/ARO/AIO-94, -04, and -12 trials, conducted in Germany) that included 1948 patients with locally advanced rectal adenocarcinoma. The CAO/ARO/AIO-94 trial recruited patients between February 1995 and September 2002, the CAO/ARO/AIO-04 trial recruited patients between July 2006 and February 2010, and the CAO/ARO/AIO-12 trial recruited patients between June 2015 and January 2018. Statistical analysis was conducted between September 2022 and March 2023., Exposures: A total of 119 of 391 patients in the CAO/ARO/AIO-94 trial group A, 295 of 1236 patients in the CAO/ARO/AIO-04 trial, and 69 of 306 in the CAO/ARO/AIO-12 trial experienced treatment failure (R2 resection or local recurrence or distant metastases) and were included in further analyses., Main Outcomes and Measures: Characteristics of treatment failure and overall survival were assessed in all 3 trial cohorts., Results: Of the 1948 patients treated in the 3 trials, 15 were excluded because of missing data. Of the remaining 1933 patients (median age, 62.5 years [range, 19-84 years]; 1363 men [71%] and 570 women [29%]) with locally advanced rectal adenocarcinoma (cT3 or 4 or cN+) treated within 3 consecutive clinical trials, 483 experienced treatment failure and were analyzed. After a median follow-up of 36 months (IQR, 24-51 months) for all patients, overall survival after treatment failure was significantly improved in the CAO/ARO/AIO-04 trial (at 3 years, 44% [IQR, 37%-51%]; hazard ratio [HR], 0.61 [95% CI, 0.47-0.79]) and further improved in the CAO/ARO/AIO-12 trial (at 3 years, 73% [IQR, 60%-87%]; HR, 0.32 [95% CI, 0.18-0.54]) compared with the CAO/ARO/AIO-94 trial (at 3 years, 30% [IQR, 22%-39%]) (both P < .001). Distant metastasis was the main reason for treatment failure throughout a 5-year follow-up (range, 67%-87%), and the relative risk for treatment failure was highest in the first 18 months in all 3 trials. ypTNM stage was significantly associated with the risk and time interval to treatment failure. Improvement in overall survival after treatment failure was independent of sex., Conclusions and Relevance: This cohort study suggests that advancements in salvage strategies during the past decades have likely improved overall survival among patients with rectal cancer who experienced treatment failure.

Introduction: Body surface area (BSA)-based dosing of 5-fluorouracil (5-FU) results in marked inter-individual variability in drug levels, whereas determination of plasma 5-FU concentration and area under the curve (AUC) is a more precise dosing method but has not been integrated into clinical routine. We conducted a multicenter, prospective study to study 5-FU AUC distributions and assess clinical factors predicting therapeutic dosing in patients receiving BSA-dosed 5-FU., Methods: Between June 2017 and January 2018, a total of 434 patients receiving continuous, infusional BSA-dosed 5-FU from 37 sites in Germany were included. Plasma 5-FU concentration and AUC were measured in venous blood samples at steady state. The primary objective was to determine 5-FU AUC distributions in relation to the target range, which is defined as 20-30 mg × h/l. The second objective was to explore clinical parameters that correlate with achievement of 5-FU AUC target range., Results: The primary tumor was mainly located in the gastrointestinal tract (96.3%), with colorectal cancer being the most common (71.2%) tumor entity. 5-FU was administered as monotherapy (8.1%) or as part of FOLFOX (33.2%), FOLFIRI (26.3%), or other regimens (12.4%). Treatment setting was adjuvant (31.3%) or metastatic (64.5%). The median AUC was 16 mg × h/l. Only 20.3% of patients received 5-FU treatment within the target range, whereas the majority of patients (60.6%) were underdosed and 19.1% of patients were overdosed. In the univariate logistic regression, treatment setting was the only clinical parameter that significantly correlated with achievement of the target range. Patients treated in the metastatic setting had a 2.1 (95% confidence interval 1.186-3.776, P = 0.011) higher odds to reach the target range compared with patients treated in the adjuvant setting., Conclusions: The majority of patients received suboptimal doses of 5-FU using BSA dosing. Therapeutic drug monitoring of 5-FU is an option for optimized individualized cancer therapy and should be integrated into the clinical practice., Competing Interests: Disclosure RDH has received honoraries for lectures and/or ad hoc advisory boards from Amgen, Astra-Zeneca, Bayer, Bristol Myers Squibb, Daiichi, Leo Pharma GmbH, Lilly, medac, Merck KGaA, Merck Sharp & Dohme, Nordic, Pierre-Fabre, Roche, Saladax, Sanofi, and Servier. MK has served on advisory boards for Novartis, BeiGene, Janssen, and Alexion. All other authors have declared no conflicts of interest. Data sharing The data that support the findings of this study are available from the corresponding author upon reasonable request., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Providing state-of-the-art palliative care is crucial in all areas of in- and outpatient settings. Studies on the implementation of palliative care standards for dying patients are rare., Methods: N = 141 physicians from all internal departments were polled anonymously about the treatment of dying patients using a self-designed questionnaire. Furthermore, we evaluated the terminal care of n = 278 patients who died in internal medicine departments at University Hospital Mannheim between January and June, 2019 based on clinical data of the last 48 h of life. We defined mandatory criteria for good palliative practice both regarding treatment according to patients' records and answers in physicians' survey., Results: Fifty-six physicians (40%) reported uncertainties in the treatment of dying patients (p < 0.05). Physicians caring for dying patients regularly stated to use sedatives more frequently and to administer less infusions (p < 0.05, respectively). In multivariate analysis, medical specialization was identified as an independent factor for good palliative practice (p < 0.05). Physicians working with cancer patients regularly were seven times more likely to use good palliative practice (p < 0.05) than physicians who did not. Cancer patients received good palliative practice more often than patients dying from non-malignant diseases (p < 0.05)., Conclusion: Guideline-based palliative care for dying patients was found to be implemented more likely and consistent within the oncology department. These results point to a potential lack of training of fellows in non-oncological departments in terms of good end-of-life care., (© 2021. The Author(s).)

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%., Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring., (© 2020 S. Karger AG, Basel.)

Purpose: Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established., Patients and Methods: We conducted a multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity., Results: Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37% v 27%) and compliance with CRT higher in group B (91%, 78%, and 76% v 97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90 v 45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B ( P  < .001), but not group A ( P = .210), fulfilled the predefined statistical hypothesis., Conclusion: Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.

Purpose: Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine., Patients and Methods: Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses., Results: A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment., Conclusion: This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine., (© 2015 by American Society of Clinical Oncology.)

Background: An increasing number of surveys have investigated professional stress and satisfaction among oncologists. Coevally, structural development has changed the oncological working environment. This survey investigated the quality of life and job stress among German oncological physicians., Methods: A 48-item questionnaire, which included the 'Stress questionnaire of physicians and nurses' (FBAS), was developed by the 'Quality of life' working group of the Internal oncology study group (AIO), and distributed anonymously at the annual meeting of the AIO working group in 2010. Descriptive statistics as well as univariate and multivariate analysis were performed., Results: 261 oncologists, mostly male (64%), older than 40 years (38%), and medical specialists (78%), took part in the survey. 'Structural conditions' were identified as causing the highest mean stress levels, followed by 'professional and private life'. Female participants showed a significantly lower global quality of life than male participants (p = 0.020). 'Structural conditions' induced more stress among younger oncologists < 50 years old (p < 0.001). Qualification status was influenced by gender (p < 0.001); the multivariate analysis described the dependence of gender (p = 0.0045), working situation (p = 0.0317) and global stress (p = 0.0008)., Conclusion: Structural conditions, age younger than 50 years and female gender were identified as stress risk factors among the AIO members, and showed that job stress is present in German oncology. Further research is warranted to develop evidence-based intervention strategies. © 2015 S. Karger GmbH, Freiburg.

Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy., Patients and Methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS)., Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47  %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44  %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed., Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

Background: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors., Methods: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated., Results: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%. The median overall survival (OS) was 59 days. 53% of the patients died at the palliative care unit. In the Cox proportional hazards model, 8 parameters indicated an unfavourable outcome: anorexia/nausea, disordered mental status, elevated lactate dehydrogenase, γ-glutamyltransferase, leukocyte count, hypoalbuminaemia, anaemia and hypercalcaemia. Based on these parameters 3 risk groups were defined: low risk (0-2 factors), intermediate risk (3-5 factors), and high risk (6-8 factors). Median survival for high-risk group was 13 days, for intermediate group 61 days, and for low-risk patients 554 days (p < 0.0001)., Conclusion: Weakness/fatigue, pain and anorexia were the main symptoms leading to the hospitalisation of patients with gynaecological malignancies. Symptom and pain control was accomplished in 80% of cases. 8 parameters were identified as indicating a poor outcome, and patients showing at least 6 or more of these factors had a very limited prognosis. Although studied retrospectively, these results may be helpful for individual treatment decisions in patients with advanced gynaecological malignancies. Prospective data and the introduction of documentation systems could help to gain more powerful knowledge about the quality of palliative care., (© 2013 S. Karger GmbH, Freiburg.)

Background: Quality of life (QoL) is frequently investigated as a secondary endpoint in clinical trials but is rarely evaluated in clinical practice. The present survey sought to assess the QoL of patients with advanced gastrointestinal tumours receiving palliative chemotherapy. Furthermore, we wanted to compare the results of subscales of the generic EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, version 3.0) using assessment tools with an emphasis on pain and depression., Patients and Methods: 150 patients with gastrointestinal tumours undergoing palliative chemotherapy completed 3 questionnaires. QoL was assessed using the EORTC QLQ-C30, Beck depression inventory (BDI) was utilised to measure the severity of patients' depression and a visual analogue scale (VAS) was applied to measure patient's pain intensity. Correlations between these assessments were calculated., Results: The survey revealed that treatment of pain and depression appeared to be inadequate in the present cohort of patients with metastatic gastrointestinal cancer. Good correlations between EORTC QLQ-C30 subscales and the VAS (r = 0.86), as well as the BDI (r = 0.63) were found., Conclusion: The present analysis indicates the need for better symptom control regarding the examples 'pain' and 'depression'. In view of the good correlation between the EORTC QLQ-C30 and the BDI and VAS, further studies on the implementation of the EORTC QLQ-C30 as a screening tool, or for follow-up measurements in daily practice are warranted., (Copyright © 2013 S. Karger AG, Basel.)

Background: Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine., Methods: This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy, in patients aged 18 years or older with pathological stage II-III locally advanced rectal cancer from 35 German institutions. Patients in the capecitabine group were scheduled to receive two cycles of capecitabine (2500 mg/m(2) days 1-14, repeated day 22), followed by chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) days 1-38), then three cycles of capecitabine. Patients in the fluorouracil group received two cycles of bolus fluorouracil (500 mg/m(2) days 1-5, repeated day 29), followed by chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 mg/m(2) daily), then two cycles of bolus fluorouracil. The protocol was amended in March, 2005, to allow a neoadjuvant cohort in which patients in the capecitabine group received chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) daily) followed by radical surgery and five cycles of capecitabine (2500 mg/m(2) per day for 14 days) and patients in the fluorouracil group received chemoradiotherapy (50·4 Gy plus infusional fluorouracil 1000 mg/m(2) days 1-5 and 29-33) followed by radical surgery and four cycles of bolus fluorouracil (500 mg/m(2) for 5 days). Patients were randomly assigned to treatment group in a 1:1 ratio using permuted blocks, with stratification by centre and tumour stage. The primary endpoint was overall survival; analyses were done based on all patients with post-randomisation data. Non-inferiority of capecitabine in terms of 5-year overall survival was tested with a 12·5% margin. This trial is registered with ClinicalTrials.gov, number NCT01500993., Findings: Between March, 2002, and December, 2007, 401 patients were randomly allocated; 392 patients were evaluable (197 in the capecitabine group, 195 in the fluorouracil group), with a median follow-up of 52 months (IQR 41-72). 5-year overall survival in the capecitabine group was non-inferior to that in the fluorouracil group (76% [95% CI 67-82] vs 67% [58-74]; p=0·0004; post-hoc test for superiority p=0·05). 3-year disease-free survival was 75% (95% CI 68-81) in the capecitabine group and 67% (59-73) in the fluorouracil group (p=0·07). Similar numbers of patients had local recurrences in each group (12 [6%] in the capecitabine group vs 14 [7%] in the fluorouracil group, p=0·67), but fewer patients developed distant metastases in the capecitabine group (37 [19%] vs 54 [28%]; p=0·04). Diarrhoea was the most common adverse event in both groups (any grade: 104 [53%] patients in the capecitabine group vs 85 [44%] in the fluorouracil group; grade 3-4: 17 [9%] vs four [2%]). Patients in the capecitabine group had more hand-foot skin reactions (62 [31%] any grade, four [2%] grade 3-4 vs three [2%] any grade, no grade 3-4), fatigue (55 [28%] any grade, no grade 3-4 vs 29 [15%], two [1%] grade 3-4), and proctitis (31 [16%] any grade, one [<1%] grade 3-4 vs ten [5%], one [<1%] grade 3-4) than did those in the fluorouracil group, whereas leucopenia was more frequent with fluorouracil than with capecitabine (68 [35%] any grade, 16 [8%] grade 3-4 vs 50 [25%] any grade, three [2%] grade 3-4)., Interpretation: Capecitabine could replace fluorouracil in adjuvant or neoadjuvant chemoradiotherapy regimens for patients with locally advanced rectal cancer., Funding: Roche Pharma AG (Grenzach-Wyhlen, Germany)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Randomized studies proved the efficacy of new drugs for the systemic treatment of advanced gastric cancer in the past 5 years. However, little is known about the use of firstline chemotherapy in clinical practice in patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (AEG) and the stomach. We investigated temporal trends in therapy and factors influencing treatment decisions for these patients during a 4-year period., Patients and Methods: 1058 patients (median age 67 years) with advanced AEG or gastric cancers undergoing treatment decisions were documented with the Therapiemonitor® in 2006-2009. Therapiemonitor collects population-based data regarding treatment decisions and strategies. Time trends of drug use and intensity in the first-line treatment were analyzed in the entire patient group and according to age (cut-off 65 years) and Karnofsky performance status (KPS; cut-off 80%)., Results: Over time, the use of oxaliplatin and docetaxel as well as capecitabine increased while cisplatin and irinotecan use slightly declined. The use of chemotherapy triplets rose from 10.1% in 2006 to 47.0% in 2009. Treatment patterns significantly varied by age and KPS: Older patients were significantly less likely to receive chemotherapy triplets, cisplatin and docetaxel but tended to more often receive oxaliplatin. Likewise, triplets, cisplatin and docetaxel were less frequently used in patients with KPS < 80%, while capecitabine and irinotecan were significantly more often used in this patient group., Conclusions: A clear tendency towards the use of more intensive chemotherapy regimens in patients with AEG and gastric cancer was observed over time. Older or less fit patients were treated preferably with monotherapy or chemotherapy doublets during 2006-2009. Oxaliplatin and docetaxel use has substantially risen., (Copyright © 2010 S. Karger AG, Basel.)

Background: Few data have been published about terminally ill patients with gastrointestinal tumors treated in palliative care units., Patients and Methods: We analyzed the data of 737 admissions of 435 patients that were treated in a palliative care unit, and tried to identify prognostic factors for survival., Results: Most frequent diagnoses at admission were colorectal, gastric, esophageal, and pancreatic cancer. Major clinical symptoms were pain (66.9%), anorexia (60.8%), weight loss (39.2%), and nausea/vomiting (36.6%). In 71.6% of the patients, morphine derivatives were administered. In 33.0% of cases, red blood cell transfusions were applied, parenteral nutrition was given in 31.3%. Median survival, calculated from the day of first hospitalization, was 35 days. On univariate analysis, several clinical and laboratory parameters were identified as prognostically important factors. In the multivariate Cox regression analysis, 5 parameters were significant: ascites and anorexia, elevated leukocyte count and lactate dehydrogenase activity, as well as decreased albumine levels. Using these parameters, patients were divided into 3 risk groups: low-risk (presence of 0-1 factors), intermediate risk (2-3 factors), and poor-risk patients (4-5 factors). Median survival for poor-risk patients was 18 days, intermediate- and low-risk patients survived 43 and 136 days, respectively (p < 0.0001)., Conclusion: In multivariate analysis, 5 prognostic factors were identified, and 3 patient groups were defined. After multicenter validation, these factors may help to guide treatment decisions in terminally ill patients with gastrointestinal tumors., (Copyright 2009 S. Karger AG, Basel.)

Background: Increasing the rate of pathological complete remissions after neoadjuvant chemoradiation of rectal cancer has become a strategy to further improve the long-term oncological outcome of patients. This report evaluates the influence of preoperative intensified radiochemotherapy on the rate and outcome of surgical complications., Materials and Methods: Patients with primary rectal cancer at stages cT3/4cNx or N+ without metastasis were preoperatively treated either with capecitabine and irinotecan or with capecitabine, irinotecan and ceutximab with a concurrent radiation (50.4 Gy). Surgery was scheduled 4-7 weeks after completion of the chemoradiation. Perioperative complications were prospectively documented during the patient's hospital stay., Results: Fifty-nine patients (median age 60; male/female: 46/13) undergoing surgery at a single center were analysed. The median distance of the tumour from the dentate line was 5 cm. The operations performed were low anterior resection (n=45), Hartmann's procedure (n=4) and abdominoperineal resection (n=10). Total mesorectal excision with R0-resection was accomplished in all but one patients. Histopathological regression was described in four grades (0-3) as defined by the Japanese Society for Cancer of the Colon and Rectum. Tumors were called major responsive when assigned to the regression grades 3 or 2, and minor or nonresponsive at regression grades 1 or 0. In total, 33 patients (55.9%) had a regression grade 2 or 3. Among them, 12 patients showed a pathological complete response without any residual cancer cell (20.3%). Seven out of 45 patients (15.5%) with sphincter-preserving surgery suffered from suture breakdown; they all had previously shown a major response of the resected tumor. Two of them died during the hospital stay., Conclusions: While in general, patients undergoing neoadjuvant intensified treatment suffer from a slight increase in surgical complications, this is markedly enhanced in patients with good treatment responses. Our results underline the oncological benefit of intensified neoadjuvant chemoradiation, but the severity of complications in low rectal anastomosis of patients with good response after neoadjuvant therapy should alert surgeons and oncologists.

Background: In a phase III study recruiting patients with stage II colon cancer the effect of adjuvant therapy with edrecolomab, a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, was compared to observation alone., Patients and Methods: From January 1997 until July 2000 a total of 377 patients were postoperatively stratified according to tumor stage (T3 vs. T4) and center, and randomly allocated to either treatment with edrecolomab (cohort A, n = 183) or observation (cohort B, n = 194). Patients in cohort A received a total of 900 mg edrecolomab. The study was terminated prematurely because of discontinuation of drug supply in Germany., Results: 305 patients were eligible for the primary endpoint of overall survival and 282 patients for disease-free survival. After a median follow-up of 42 months overall survival and disease-free survival were not significantly different. Toxicity was mild., Conclusions: In the present study, postoperative adjuvant treatment with edrecolomab in patients with resected stage II colon cancer did not improve overall or disease-free survival.

Background: Weekly infusional 5-fluorouracil (5-FU) and folinic acid (FA) as part of multi-drug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective with low toxicity. The present analysis was carried out to evaluate the safety and efficacy of 5-FU/FA in combination with 3-weekly mitomycin C (MMC) in patients with advanced gastric cancer., Patients and Methods: A total of 28 patients with AGC were analysed (first line n=23). They received weekly 24-h 5-FU 2,600 mg/m2 preceded by 2-h FA 500 mg/m2 for 6 weeks followed by a two week rest period. Bolus MMC 10 mg/m2 was applied on days 1 and 22. Patient characteristics were: m/f 17/11; median age 67 years (43-79). The most common metastatic sites were liver and peritoneum (n=12, respectively)., Results: A median of 3 and a total of 91 cycles were administered. Mean dose intensity in cycle I was: 5-FU 86%, MMC 87%. Responses were observed in 43%, no change was seen in 29% of the patients. Median overall survival was 9.7 months (10.7 months for patients treated first line). Non-haematological toxicities (NCI CTC grades 3 and 4) were observed in 2 patients, leukopenia and thrombocytopenia grades 3/4 were observed in 50 and 25% of the patients, respectively., Conclusions: Infusional 5-FU/FA plus MMC may safely be used in patients with AGC in the routine clinical setting. This regimen yields response rates and survival data comparable to platinum-based regimen.

Aim: Objective of this study was to evaluate the hemoglobin level (Hb) as potential prognostic factor in uniformly staged patients (pts) undergoing primary chemoradiotherapy (ChRT) for locally advanced squamous cell carcinoma (SCC) of the esophagus., Patients and Methods: Pts with histologically proven SCC of the esophagus (uT3/4 Nx or uTx N+) were included in the analysis. Staging procedures comprised endoscopic ultrasound, barium swallow and computed tomography. All pts received radiotherapy (> or =40 Gy) and > or =2 courses of fluorouracil/folinic acid, and cisplatin (5 days/month). In selected pts surgical resection after neoadjuvant ChRT was carried out. Clinical parameters, especially Hb were retrospectively evaluated for their impact on survival., Results: 46 pts were treated between 1996 and 2001. Median survival was 16 months. Survival for pts treated with definitive ChRT (n = 28) was 14 months, whereas pts treated surgically after neoadjuvant ChRT (n = 18) survived 19 months (p = 0.79). Pts with low Hb levels at baseline did not show a worse outcome in comparison with pts with normal Hb levels (16 months), whereas a significant decrease in Hb level within the time period of ChRT was associated with a significantly inferior outcome (11 vs. 31 months; p = 0.046). Pts requiring blood transfusion tended to have inferior survival (11 vs. 24 months; p = 0.07)., Conclusion: In this retrospective analysis a significant decrease of Hb level during ChRT was identified as prognostic factor for pts undergoing ChRT of SCC of the esophagus., (Copyright 2004 S. Karger GmbH, Freiburg.)