MAGIC Trials Research Articles

Prognostic and predictive impact of sex in locally advanced microsatellite instability high gastric or gastroesophageal junction cancer: An individual patient data pooled analysis of randomized clinical trials

BackgroundSurgery plus peri-operative/adjuvant chemotherapy is the standard of care for locally advanced GC/GEJC, though with unsatisfactory results. dMMR/MSI-high tumors have better prognosis and scant benefit from chemotherapy as compared to pMMR/MSS ones. The differential outcome of therapies in terms of safety and efficacy according to sex is still debated in GC/GEJC patients. MethodsWe previously performed an individual patient data pooled analysis of MAGIC, CLASSIC, ITACA-S, and ARTIST trials including GC/GEJC patients treated with surgery alone or surgery plus peri-operative/adjuvant chemotherapy to assess the value of MSI status. We performed a secondary analysis investigating the prognostic and predictive role of sex (female versus male) in the pooled analysis dataset in the overall population and patients stratified for MSI status (MSI-high versus MSS/MSI-low). Disease-free (DFS) and overall survival (OS) were calculated. ResultsPatients with MSI-high tumors had improved survival as compared to MSS/MSI-low ones irrespective of sex, whereas in those with MSS/MSI-low tumors, females had numerically longer OS and DFS (5-year OS was 63.2% versus 57.6%, HR 0.842; p = 0.058, and 5-year DFS was 55.8% versus 50.8%, HR 0.850; p = 0.0504 in female versus male patients). The numerical difference for the detrimental effect of chemotherapy in MSI-high GC was higher in females than males, while the significant benefit of chemotherapy over surgery alone was confirmed in MSS/MSI-low GC irrespective of sex. ConclusionsThis pooled analysis including four randomized trials highlights a relevant impact of sex in the prognosis and treatment efficacy of MSI-high and MSS/MSI-low non-metastatic GC/GEJC.

Stroma AReactive Invasion Front Areas (SARIFA) improves prognostic risk stratification of perioperative chemotherapy treated oesophagogastric cancer patients from the MAGIC and the ST03 trial.

Tumour-associated fat cells without desmoplastic stroma reaction at the invasion front (Stroma AReactive Invasion Front Areas (SARIFA)) is a prognostic biomarker in gastric and colon cancer. The clinical utility of theSARIFA status in oesophagogastric cancer patients treated with perioperative chemotherapy is currently unknown. TheSARIFA status was determined in tissue sections from patients recruited into the MAGIC (n = 292) or ST03 (n = 693) trials treated with surgery alone (S, MAGIC) or perioperative chemotherapy (MAGIC, ST03). The relationship between SARIFA status, clinicopathological factors, overall survival (OS) and treatment was analysed. TheSARIFA status was positive in 42% MAGIC trial S patients, 28% MAGIC and 48% ST03 patients after pre-operative chemotherapy. SARIFA status was related to OS in MAGIC trial S patients and was an independent prognostic biomarker in ST03 trial patients (HR 1.974, 95% CI 1.555-2.507, p < 0.001). ST03 patients with lymph node metastasis (ypN + ) and SARIFA-positive tumours had poorer OS than patients with ypN+ and SARIFA-negative tumours (plogrank < 0.001). TheSARIFA status has clinical utility as prognostic biomarker in oesophagogastric cancer patients irrespective of treatment modality. Whilst underlying biological mechanisms warrant further investigation, theSARIFA status might be used to identify new drug targets, potentially enabling repurposing of existing drugs targeting lipid metabolism.

Neoadjuvant and adjuvant therapy in esophageal cancer.

Esophageal cancer is an aggressive malignancy that carries a high mortality rate. The treatment of locally advanced resectable esophageal cancer requires a multimodal approach involving chemotherapy, radiation therapy, and surgical resection. Optimal treatment combinations and sequences for squamous cell carcinoma (SCC) versus adenocarcinoma (AC) histological subtypes are still being determined. For very early stage esophageal cancers, endoscopic therapies or surgical resection without chemotherapy and radiation are preferred. Neoadjuvant chemoradiation followed by surgical resection has been the standard in locally advanced resectable esophageal cancer based on the landmark CROSS trial. Definitive chemoradiation is recommended for patients who are not surgical candidates or decline surgery. Perioperative chemotherapy without radiation can be considered for lower esophageal AC and gastroesophageal (GE)-junction AC based on landmark MAGIC and FLOT4 trials. Additional trials are underway to compare preoperative chemoradiation to perioperative chemotherapy in esophageal and GE-junction ACs. Thus far, targeted therapies against vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor 2 (HER2) have not been successful in the neoadjuvant/adjuvant setting. The roll of immunotherapy in perioperative/adjuvant setting is promising. Based on the CheckMate 577 trial, adjuvant nivolumab should be considered for all patients following neoadjuvant chemoradiation and R0 resection with residual pathologic disease. Additional trials involving various immunotherapy agents are underway.

Imperial Crisis Response and the Antiochene Magic and Treason Trials of 372 CE

The writings of Ammianus Marcellinus, Libanius, and John Chrysostom have enshrined the Antiochene treason and magic investigations conducted under Emperor Valens in 372 CE as a testament to the ruler’s excessive paranoia and poor relationship with the eastern metropolis. By reexamining these three authors’ allegations of judicial corruption and abusive policing during the trials, this article contends that Valens’s response to the crisis was leveraged with far more legality, moderation, and success than often discussed. The rigorous tactics implemented during the trials demonstrate Valens and his administration’s intent to counter potential sedition among Antioch’s citizenry with the full brunt of Roman law and military action. Comparisons with legal precedents reveal, however, that Valens’s administration balanced these stern deterrents with deference to the law and attempted to assuage Antiochene interests throughout the investigations. Antiochene lobbying efforts were also more impactful in mitigating the imperial response, as demonstrated by Chrysostom’s account of a public protest that successfully petitioned Valens to pardon one of the accused. This article concludes that this pardon and Valens’s application of moderated or commuted sentences throughout the trials indicate his efforts to maintain a constructive imperial-urban relationship with the Antiochene populace. This conclusion not only forces a reconsideration of Valens’s relationship with his de facto imperial capital throughout the trials but also indicates the dangers of relying too heavily on literary interpretations of Valens’s reign.

Neoadjuvant Treatment Strategies for Resectable Proximal Gastric, Gastroesophageal Junction and Distal Esophageal Cancer.

Simple SummaryThe five-year survival for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer ranges from 30 to 60% globally. Neoadjuvant and/or perioperative therapy has emerged as a treatment tool to improve patient selection for surgery, resectability, and locoregional control of the disease. As a result, treatment strategies have evolved from the first trials in the late 1980s to the pivotal CROSS trial updated in 2015. The review summarizes current clinical trials and treatment recommendations with regard to neoadjuvant and/or perioperative therapy for patients with adenocarcinoma and squamous cell carcinoma of the distal esophagus, GEJ, and proximal stomach.Neoadjuvant treatment strategies for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer have evolved over several decades. Treatment recommendations differ based on histologic type—squamous cell carcinoma (SCC) versus adenocarcinoma (AC)—as well as the exact location of the tumor. Recent and older clinical trials in this area were critically reviewed. Neoadjuvant chemoradiation with concurrent taxane- or fluoropyrimidine-based chemotherapy has an established role for both AC and SCC of the distal esophagus and GEJ. The use of perioperative chemotherapy for gastric AC is based on the FLOT4 and MAGIC trials; however, the utility of neoadjuvant chemoradiation in this setting requires further evaluation. Additional clinical trials evaluating chemotherapy, targeted therapy, immunotherapy, and radiation that are currently in process are highlighted, given the need for further disease control.

Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial

The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial. The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival. Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P= 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios. After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186).

Lack of National Adoption of Evidence-Based Treatment for Resectable Gastric Adenocarcinoma

BackgroundLevel 1 evidence for multimodal treatment of resectable gastric adenocarcinoma from the Intergroup 0116 (2001) and MAGIC (2006) trials demonstrated survival benefit of adjuvant chemoradiation (CRT) and perioperative chemotherapy, respectively. We evaluated the adoption of evidence-based treatment in the post-MAGIC era and its impact on survival. MethodsA total of 7058 patients with resectable gastric adenocarcinoma undergoing definitive surgical resection between 2004 and 2015 were analyzed using the National Cancer Database. ResultsOver the study period, the proportion of patients receiving adjuvant CRT decreased from 19.1% to 9.1%, while perioperative chemotherapy increased from 1.9% to 28.6%. Utilization of perioperative chemotherapy surpassed adjuvant CRT in 2011. Evidence-based treatment (either perioperative chemotherapy or adjuvant CRT) had better overall survival (OS) than other treatments for clinical stage II–III patients (p < 0.05). On multivariate analysis of the whole study period, evidence-based treatments were associated with better OS (HR 0.67 [0.60–0.74], p < 0.05). Only 360/1262 (28.5%) patients in the perioperative chemotherapy group completed postoperative therapy, which was associated with improved OS (p < 0.05). For clinical stage III patients (n = 2402), only 806 (33.6%) received evidence-based treatment, while 487 (22.2%) underwent surgery alone. On multivariate analysis of these patients between 2010 and 2015, both perioperative chemotherapy (HR 0.49 [0.35–0.68]) and adjuvant CRT (HR 0.31 [0.21–0.44]) were associated with better OS than surgery alone (p < 0.05). ConclusionsSince the INT-0116 and MAGIC trials, utilization of evidence-based treatments for resectable gastric adenocarcinoma has increased, with perioperative chemotherapy surpassing adjuvant CRT as the preferred practice. However, overall utilization of these regimens remains quite low nationally despite association with improved OS.

Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.

In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value. We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery v surgery) with MSI. MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio [HR], 1.88; 95% CI, 1.28 to 2.76; P < .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73; P = .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12). In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.

Management of Locally Advanced and Metastatic Esophageal Cancer in the Older Population.

This review aims to synthesise the current literature on the management of early-stage and metastatic esophageal cancers, focusing on the older population. In particular, we aim to dissect out the elderly-specific data from the relevant trials and to discuss the issues unique to this population. While surgery is the curative modality in esophageal malignancies, the CROSS, MAGIC and FLOT trials demonstrate a clear advantage to neoadjuvant therapy (chemotherapy and chemoradiotherapy). These trials, however, included few elderly patients. There is a similar lack of elderly-specific data in the metastatic setting. Esophageal malignancies remain highly lethal with increasing incidence with age. Despite the relative lack of elderly-specific data, the fit older population appear to similarly benefit from multimodal therapy in early-stage and palliative therapy in metastatic disease.

The Charms of Women and Priests: Sex, Magic, Gender and Public Order in Late Medieval Italy

How did judicial authorities in late medieval Italy understand the relationship between gender, sexuality, social status, magic and public order, especially when magic was used to facilitate the crime of adultery? What might this reveal about the intersection of gender, magic and public order in a place and time so fraught with political and social tensions? This study qualitatively compares four love‐magic trials from fourteenth‐century Lucca and suggests that the anxieties underpinning these trials were both particular to late medieval Italian communes and projected onto two populations, women and priests, whose unchecked sexuality posed the greatest threat to civic order. Historians examining gender in medieval European magic trials have often treated judicial officials’ anxieties as portents of the ‘witch craze’ of early modern Europe. Historians of medieval Lucca have tended to treat the political and gender histories of the city as largely separate. This article suggests that the courts’ increasing regulation of gender and sexuality in late medieval Lucca reflected larger ecclesiastical and communal concerns about the dissolution of civic order. In a world of civic power that increasingly belonged to secular men, the unchecked sexuality of women and clergy represented a dual threat to the stability of the family and, by extension, the city. This article argues that secular and ecclesiastical judicial officials feared not magic itself, but the ability of magic to invert power relations between men and women and between clergy and laity, destroying public order.

Neoadjuvant therapy for gastroesophageal adenocarcinoma.

Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions.

D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

BackgroundPatients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT) following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature.MethodsAnalysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperative outcomes and histopathological responses to NACT were analyzed. The data is presented and compared to a cohort of patients undergoing upfront surgery in the same time period.ResultsIn this study, 139 patients (42 female and 97 male patients, median age 53 years) with gastric adenocarcinoma received NACT. Chemotherapy-related toxicity was noted in 32% of patients. Of the 139 patients, 129 underwent gastrectomy with D2 lymphadenectomy, with 12% morbidity and no mortality. Major pathological response of primary tumor was noted in 22 patients (17%). Of these 22 patients, lymph node metastases were noted in 12 patients. The median blood loss and lymph node yield was not significantly different to the 62 patients who underwent upfront surgery. Patients who underwent upfront surgery were older (58 vs. 52 years, P <0.02), had a higher number of distal cancers (63% vs. 82%, P <0.015) and a longer hospital stay (11 vs. 9 days, P <0.001).ConclusionsPerioperative outcomes of gastrectomy with D2 lymphadenectomy for locally advanced, resectable gastric cancer were not influenced by NACT. The number of lymph nodes harvested was unaltered by NACT but, more pertinently, metastases to lymph nodes were noted even in patients with a major pathological response of the primary tumor. D2 lymphadenectomy should be performed in all patients irrespective of the degree of response to NACT.

Fortunetellers and Sorcerers in the Service of a Russian Aristocrat of the Eighteenth Century: The Case of Chamberlain Petr Saltykov

The case of Petr Saltykov, which stretched on between 1758 and 1765, with a surprising coda in 1796, is noteworthy in many respects. The material collected in connection with Saltykov’s crime is useful for an investigation into magic belief as such, offering parallels and supplementary information to the dozens of “magic trials” of the 18th century. However, what makes the Saltykov case unique is how the chancellor’s “superstition” managed so compellingly to bring together two cultures – traditional folk culture and the “Europeanized” culture of the imperial court. The case of Saltykov’s “sorcery” brought the diametrically opposed cultures of the court elite and the masses into confrontation. But even opposites can come together. As it turned out, the magic beliefs of the masses and medical practices of archaic traditional culture continued to attract adherents at court, getting along just fine in a high-culture, “Europeanized” environment. The chasm that lay between the culture of the aristocratic court elite and popular culture in the 18th century was not unbridgeable, although possible intersections of these two cultures sometimes took on rather strange configurations.

TOPGEAR: An international randomized phase III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer (AGITG/TROG/EORTC/NCIC CTG).

TPS4141 Background: Optimal management of patients with resectable gastric cancer remains unknown. Since the INT0116 and MAGIC trials, there are 2 standards of care for adjuvant therapy: postoperative chemoradiotherapy (CRT) and perioperative ECF chemotherapy. The important question arising from these studies is whether CRT is superior to chemotherapy alone as adjuvant therapy. This randomized phase II/III trial will compare CRT to chemotherapy alone in the preoperative setting. Methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either preoperative chemotherapy alone (ECFx3 as per MAGIC regimen) or preoperative CRT (ECFx2 followed by 45Gy of radiation with concurrent 5-FU). Following surgery, both groups will receive 3 further cycles of ECF. The trial is being conducted in two Parts; Part I (phase II component) will recruit 120 patients with the aim of demonstrating sufficient efficacy and safety of preoperative CRT, as well as trial feasibility. Part II (phase III component) will recruit a further 632 patients to provide a total of 752. The primary endpoint for Part I is pathological complete response rate, and for Part 2 it is overall survival. The trial includes formal quality of life and biological sub-studies. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. Current status: This study is an international, intergroup trial led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. To date, 36 patients have been recruited from 20 sites in Australia and New Zealand; European and Canadian sites will commence recruitment in 2012.

Magic in the Ancient Greek World

Magic in the Ancient Greek World

Effects of Racial/Social Factors and INT-0116/ MAGIC Trials Publication on Radiation Therapy (RT) Utilization for Gastric Cancer

The role of RT in the treatment of gastric cancer remains uncertain despite the findings of the INT-0116 study demonstrating local control and survival benefits with post-operative (post-op) chemoradiation therapy. The publication of the MAGIC trial suggested identical outcomes in patients treated with perioperative chemotherapy alone. We attempted to identify the impact of publication of the INT-0116 and MAGIC trials on utilization patterns of post-op RT using a large, national, population based database.

Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS)

BackgroundRadical surgery is the cornerstone in the treatment of resectable gastric cancer. The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy, respectively. Since these trials cannot be compared directly, both regimens are evaluated prospectively in the CRITICS trial. This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively.Methods/designIn this phase III multicentre study, patients with resectable gastric cancer are treated with three cycles of preoperative ECC (epirubicin, cisplatin and capecitabine), followed by surgery with adequate lymph node dissection, and then either another three cycles of ECC or concurrent chemoradiation (45 Gy, cisplatin and capecitabine). Surgical, pathological, and radiotherapeutic quality control is performed. The primary endpoint is overall survival, secondary endpoints are disease-free survival (DFS), toxicity, health-related quality of life (HRQL), prediction of response, and recurrence risk assessed by genomic and expression profiling. Accrual for the CRITICS trial is from the Netherlands, Sweden, and Denmark, and more countries are invited to participate.ConclusionResults of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European standard of perioperative chemotherapy, and will therefore play a key role in the future management of patients with resectable gastric cancer.Trial registrationclinicaltrials.gov NCT00407186

Use of perioperative therapy in gastric cancer: A retrospective comparison of ECF and chemoradiation.

112 Background: Gastric Cancer (GC) remains a major cause of cancer related morbidity and mortality in Western Countries with five year survival rates between 30%-40%. Preoperative therapy has been championed by groups extrapolating data from the Intergroup 0116 and the MAGIC trials, with a view to enhancing completion of therapy and improving survival in locally advanced tumors. Methods: Patients with preoperative treatment of GC were reviewed from our tumor registry. Stages were assigned by AJCC 7th edition. A comparison between the ECF regimen and non-ECF chemoradiation regimens was performed to view patterns of pathologic complete response (pCR), recurrence, toxicity and overall survival. Results: Forty-two patients were identified and stratified into two groups; Group 1 ECF treatment arm (n = 16) compared to group 2 non-ECF chemo-radiation arm (n = 26). No statistical difference was noted in age, ethnicity or stage stratification. All of Group 1 received their chemotherapy regimen after 2005. In contrast, 60% of Group 2 patients received their treatment pre-2005. Only 56% the ECF group completed their treatment course (19% received other postoperative therapy). Seventy percent of group 2 received adjuvant chemotherapy. A grade 2 or higher toxicity was noted in 16% of Group 1 compared to 60% in Group 2 (p = 0.035). Seven complications were noted in the group 1 compared to 10 in group 2 (p = NS). The differentiation of tumor between groups was not significant (p = 0.97). Length of stay was significant (Group 1:9 days, Group 2:12 days, p = 0.02). More nodes were retrieved from group 1 versus group 2 (20.2 versus 15.2, p = 0.03). Group 1 had 3 recurrences (19%) while Group 2 had 11 recurrences (42%, p = 0.94). In both groups 80% of recurrences were distant. Group 1 had a 19% pCR versus 23% in group 2 (p = 0.79). Two-year survival was 70% in both groups, with a median survival of 51 months for group 2. Median survival was not reached for group 1. Conclusions: No difference was noted in pCR, recurrences, or survival between these two regimens. If this can be confirmed in larger, prospective, randomized trials, use of radiation and its potential morbidity may be avoided. No significant financial relationships to disclose.

Diagnostik und Therapie des Magenkarzinoms – Workflow

This review comments on the diagnosis and treatment of gastric cancer in the classical meaning--excluding adenocarcinoma of the -oesophagogastric junction. Algorithms of diagnosis and care with respect to tumour stage are presented. PREOPERATIVE DIAGNOSIS: Besides oesophagogastroduodenoscopy, endoscopic ultrasonography is necessary for the accurate diagnosis of T categories and as a selection criterion for neoadjuvant chemotherapy. Computed tomography is recommended for preoperative evaluation of tumours > T1, laparoscopy has become an effective stag-ing tool in T3 and T4 tumours avoiding unnecessary laparotomies and improving the detection of small -liver and peritoneal metastases. Endoscopic mucosal resection and submucosal dissection are indicated in superficial cancer confined to the mucosa with special characteristics (T1 a / no ulcer / G1, 2 / Laurén intestinal / L0 / V0 / tumour size < 2 cm). In all other cases total gastrectomy or distal subtotal gastric resection are indicated, the latter in cases of tumours located in the distal two-thirds of the stomach. Standard lymphadenectomy (LAD) is the D2 LAD without distal pancreatectomy and splenectomy. The Roux-en-Y oesophagojejunostomy is still the preferred type of reconstruction. An additional pouch reconstruction should be considered in -patients with favourable prognosis, this also -applies for the preservation of the duodenal passage by jejunum interposition. Extended organ resections are only indicated in cases where a R0-resection is possible. Hepatic resection for metachronous or synchronous liver metastases is rarely advised since 50 % of patients with liver metastases show concomitant peritoneal dissemination of the disease. Undergoing gastrectomy at a high-volume centre is associated with lower in-hospital mortality and a better prognosis, however, clear thresholds for case load cannot be given. Perioperative chemotherapy and postoperative chemoradiotherapy are based on the MAGIC and MacDonald trials. Perioperative chemotherapy should be performed in patients with T3 and T4 tumours with the aim to increase the likelihood of curative R0-resection by downsizing the tumour. Adjuvant postoperative chemotherapy cannot be recommended since its benefit has so far not been proven in randomised trials. In selected patients with incomplete lymph-node dissection and questionable R0-resection postoperative chemoradiotherapy may be debated.

A Case of Witchcraft: The Trial of Urbain Grandier. By Robert Rapley. Montreal: McGill-Queen's University Press, 1998. ix + 277 pp. $29.95 cloth. - “Wicked Arts”: Witchcraft and Magic Trials in Southern Sweden, 1635–1754. By Per Sörlin. Cultures, Beliefs, and Traditions: Medieval and Early Modern Peoples 7. Leiden: Brill, 1999. viii + 239 pp. n.p.

A Case of Witchcraft: The Trial of Urbain Grandier. By Robert Rapley. Montreal: McGill-Queen's University Press, 1998. ix + 277 pp. $29.95 cloth. - “Wicked Arts”: Witchcraft and Magic Trials in Southern Sweden, 1635–1754. By Per Sörlin. Cultures, Beliefs, and Traditions: Medieval and Early Modern Peoples 7. Leiden: Brill, 1999. viii + 239 pp. n.p. - Volume 69 Issue 2