Switzerland: cancer statistics from IARC GlobalCan (2012)
|Population in 2012: ||7.7m|
|People newly diagnosed with cancer (excluding NMSC) / yr: ||42,000|
|Age-standardised rate, incidence per 100,000 people/yr: ||287.0|
|Risk of getting cancer before age 75:||28.8%|
|People dying from cancer /yr: ||16,400|
Menu: Swiss Cancer Resources Swiss Cancer Organisations Recent Research Publications from Switzerland
Krebsliga Schweiz | Swiss Cancer League - Deutsch - Translate to English
A national, non-profit organisation, founded in 1910.
Scientific Association of Swiss Radiation Oncology
SASRO brings together radiation oncologists, radiation physicists, radiation biologists and radiographers in Switzerland to promote excellence in the field of radiotherapy. Radiation Oncology
Arbeitsgemeinschaft für Gynäkologische Onkologie und Brustgesundheit | Swiss Association of Gynecological Oncology - Deutsch - Translate to English
swiss-AGO Gynecologic Oncology
National Institute for Cancer Epidemiology and Registration
NICER aggregates data collected by the cantonal and regional cancer registries of Switzerland. The site includes statistics and publications. Cancer Registries
Schweizerische Pädiatrische Onkologie Gruppe | Swiss Paediatric Oncology Group - Deutsch - English
SPOG is a non-profit professional organisation, involved in research to achieve better treatment options and a higher quality of life for children and adolescents suffering from cancer. Pediatric Oncology Childhood Cancer
Schweizerische Patientenorganisation für Lymphombetroffene und angehörig | Swiss Patient Organization for Lymphoma Patients - Deutsch - Translate to English
Verein für Onkologische Pharmazie | Association for Oncology Pharmacy - Deutsch - Translate to English
A a non-profit association founded 2009. Oncology Pharmacy
A two-session psychological intervention for siblings of pediatric cancer patients: a randomized controlled pilot trial
Referenced research article; open access. Alice Prchal et al. Child and Adolescent Psychiatry and Mental Health 2012, 6:3 Siblings of Children with Cancer
An international, peer-reviewed open access journal on oncology from MDPI
Frontiers in Oncology
A journal which publishes articles on the most outstanding discoveries across a wide research spectrum of Oncology. Includes specialty sections.
ISREC: Swiss Institute for Experimental Cancer Research
Based at EPFL, Lausanne
Schweizerischen Arbeitsgemeinschaft für Klinische Krebsforschung | Swiss Group for Clinical Cancer Research - Deutsch - English
SAKK is a non-profit organization and cooperative association that has been conducting multicenter clinical trials independently of the pharmaceutical industry since 1965.
Swiss Childhood Cancer Registry
A national, population-based cancer registry located at the Institute of Social and Preventive Medicine (ISPM) at the University of Bern and closely co-operates with the Swiss Paediatric Oncology Group. Cancer Registries Childhood Cancer
Switzerland - European Cancer Observatory
Incidence, mortality and prevalence data and graphs.
Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, et al.Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.
J Clin Oncol. 2013; 31(34):4333-42 [PubMed
] Related Publications
PURPOSE: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse.
PATIENTS AND METHODS: In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion).
RESULTS: N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001).
CONCLUSION: These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
Amélie Trinquand, Raouf Ben Abdelali, Etienne Lengliné, Noémie De Gunzburg, Ludovic Lhermitte, Jonathan Bond, Agnès Buzyn, Elizabeth Macintyre, and Vahid Asnafi, University Paris Descartes, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)-8...
Gilbert MR, Wang M, Aldape KD, et al.Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial.
J Clin Oncol. 2013; 31(32):4085-91 [PubMed
] Article available free on PMC
after 10/11/2014 Related Publications
Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM.PATIENTS AND METHODS:
This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status.RESULTS:
A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue.CONCLUSION:
This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.Related: Dacarbazine Temozolomide
Mark R. Gilbert, Kenneth D. Aldape, Terri S. Armstrong, Jeffrey S. Wefel, Anita Mahajan, and Paul D. Brown, University of Texas MD Anderson Cancer Center; Terri S. Armstrong, University of Texas Health Science Center-School of Nursing, Houston, TX; Meihua Wang and Minhee Won, Radiation Therapy Onco...
Terwijn M, van Putten WL, Kelder A, et al.High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study.
J Clin Oncol. 2013; 31(31):3889-97 [PubMed
] Related Publications
Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers.PATIENTS AND METHODS:
In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy).RESULTS:
After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR.CONCLUSION:
In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.Related: Acute Myeloid Leukemia (AML)
Monique Terwijn, Angèle Kelder, Peter C. Huijgens, Angelika M. Dräger, Yvonne J.M. Oussoren, Willemijn J. Scholten, Alexander N. Snel, Gert J. Ossenkoppele, and Gerrit J. Schuurhuis, VU University Medical Centre; Bart J. Biemond, Academic Medical Centre, Amsterdam; Wim L.J. van Putten, Vi...
Viganò L, Capussotti L, De Rosa G, et al.Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.
Ann Surg. 2013; 258(5):731-40; discussion 741-2 [PubMed
] Related Publications
We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy.BACKGROUND:
CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear.METHODS:
Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases.RESULTS:
A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively).CONCLUSIONS:
TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.Related: Colorectal (Bowel) Cancer Bevacizumab (Avastin) Oxaliplatin Irinotecan
Departments of *HPB and Digestive Surgery and †Pathology, Ospedale Mauriziano Umberto I, Torino, Italy; and Departments of ‡Visceral and Transplantation Surgery and §Clinical Pathology, University Hospitals, Geneva, Switzerland.
Ohtsu A, Ajani JA, Bai YX, et al.Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study.
J Clin Oncol. 2013; 31(31):3935-43 [PubMed
] Related Publications
The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer.PATIENTS AND METHODS:
Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety.RESULTS:
Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW.CONCLUSION:
Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers.Related: Stomach Cancer Gastric Cancer Everolimus (Afinitor)
Atsushi Ohtsu, National Cancer Center Hospital East, Kashiwa; Keisho Chin, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo; Kei Muro, Aichi Cancer Center Hospital, Nagoya, Japan; Jaffer A. Ajani, University of Texas MD Anderson Cancer Center, Houston, TX; Tarek Sahmoud, ...
Buchs NC, Pugin F, Volonte F, et al.Robotic transanal endoscopic microsurgery: technical details for the lateral approach.
Dis Colon Rectum. 2013; 56(10):1194-8 [PubMed
] Related Publications
BACKGROUND: Transanal endoscopic microsurgery is a minimally invasive approach reserved for the resection of selected rectal tumors. However, this approach is technically demanding. Although robotic technology may overcome the limitations of this approach, the system can be difficult to dock, especially in the lithotomy position.
OBJECTIVE: The study aim is thus to report the technical details of robotic transanal endoscopic microsurgery with the use of a lateral approach.
DESIGN AND SETTINGS: This study is a prospective evaluation of robotic transanal endoscopic microsurgery in a single tertiary institution, under a protocol approved by our local ethics committee.
INTERVENTION: Patients underwent a routine mechanical bowel preparation and were placed in the left or right lateral position according to the tumor location. A circular anal dilatator was used together with the glove port technique. The robotic system was then docked over the hip. A 30° optic and 2 articulated instruments were used with an additional assistant trocar. The tumor excision was realized with an atraumatic grasper and an articulated cautery hook, and the defect was closed with barbed continuous stiches in each case.
MAIN OUTCOME MEASURE: The primary outcome was the safety and feasibility of the procedure.
RESULTS: Three patients underwent a robotic transanal endoscopic microsurgery with the use of the lateral approach. Mean operative time was 110 minutes, including 20 minutes for the docking of the robot. There was 1 intraoperative complication (a pneumoperitoneum without intraabdominal lesion) and no postoperative complications. Mean hospital stay was 3 days. Margins were negative in all the cases.
LIMITATIONS: The study was limited by the small number of patients.
CONCLUSION: Robotic transanal endoscopic microsurgery with use of the lateral approach is feasible and may facilitate the local resection of small lesions of the mid and lower rectum. It might assume an important place in sphincter-preserving surgery, especially for selected and early rectal cancer (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A114).
Clinic for Visceral and Transplantation Surgery, Department of Surgery, University Hospital of Geneva, Geneva, Switzerland.
San-Miguel JF, Richardson PG, Günther A, et al.Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma.
J Clin Oncol. 2013; 31(29):3696-703 [PubMed
] Related Publications
Despite advancements, prognosis for patients with relapsed/refractory multiple myeloma (MM) is poor, and novel therapies are needed. Panobinostat is a potent deacetylase inhibitor that elicits synergistic effects on MM cells in combination with bortezomib. This phase Ib study sought to determine the maximum-tolerated dose (MTD) of panobinostat plus bortezomib in patients with relapsed or relapsed and refractory MM.PATIENTS AND METHODS:
In the dose-escalation phase (n = 47), panobinostat was administered orally thrice weekly every week in combination with bortezomib (21-day cycles). After MTD determination, patients were evaluated in an expansion phase (n = 15) that incorporated a 1-week treatment holiday of panobinostat, with dexamethasone added in cycle 2. Additional assessments included safety, pharmacokinetics, and efficacy per International Myeloma Working Group criteria.RESULTS:
The MTD was established at panobinostat 20 mg plus bortezomib 1.3 mg/m(2). Grade 3 or 4 adverse events (AEs) included thrombocytopenia (85.1%), neutropenia (63.8%), and asthenia (29.8%) in the escalation phase, and thrombocytopenia (66.7%), neutropenia (46.7%), and fatigue (20.0%) in the expansion phase. At MTD in the escalation phase, eight patients (47.1%) discontinued therapy as a result of AEs, whereas five patients (33.3%) discontinued treatment in the expansion phase. Expansion phase patients demonstrated greater median treatment duration. Overall response rate (ORR) was 73.3% in the expansion phase and 52.9% at the escalation phase MTD. Among bortezomib-refractory patients, the ORR was 26.3%, and 42.1% of patients had ≥ minimal response.CONCLUSION:
The MTD of panobinostat plus bortezomib was determined and demonstrated activity in patients with relapsed or relapsed/refractory MM, including bortezomib-refractory patients. A phase II/III clinical trial program (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma [PANORAMA]) has been initiated.Related: Myeloma Bortezomib
Jesús F. San-Miguel and María Victoria Mateos, Servicio e Hematologia, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Institut de Bilogia Molecular de Barcelona (Universidad de Salamanca-Spanish National Research Council), Salamanca; Joan...
von Minckwitz G, Blohmer JU, Costa SD, et al.Response-guided neoadjuvant chemotherapy for breast cancer.
J Clin Oncol. 2013; 31(29):3623-30 [PubMed
] Related Publications
We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer.PATIENTS AND METHODS:
We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery.RESULTS:
DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor-positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor-negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74).CONCLUSION:
This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor-positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.Related: Breast Cancer
Gunter von Minckwitz, Keyur Mehta, and Sibylle Loibl, Headquarters, German Breast Group, Neu-Isenburg; Jens Uwe Blohmer, St Gertrauden Krankenhaus, Berlin); Serban Dan Costa, Universitäts-Frauenklinik, Magdeburg; Carsten Denkert, Institute for Pathology, Charite, Berlin; Holger Eidtmann, Unive...
Tschuor Ch, Croome KP, Sergeant G, et al.Salvage parenchymal liver transection for patients with insufficient volume increase after portal vein occlusion -- an extension of the ALPPS approach.
Eur J Surg Oncol. 2013; 39(11):1230-5 [PubMed
] Related Publications
Portal vein ligation (PVL) or embolization (PVE) are standard approaches to induce liver hypertrophy of the future liver remnant (FLR) prior to hepatectomy in primarily non-resectable liver tumors. However, this approach fails in about one third of patients. Recently, the new "ALPPS" approach has been described that combines PVL with parenchymal transection to induce rapid liver hypertrophy. This series explores whether isolated parenchymal transection boosts liver hypertrophy in scenarios of failed PVL/PVE.METHODS:
A multicenter database with 170 patients undergoing portal vein manipulation to increase the size of the FLR was screened for patients undergoing isolated parenchymal transection as a salvage procedure. Three patients who underwent PVL/PVE with subsequent insufficient volume gain and subsequently underwent parenchymal liver transection as a salvage procedure were identified. Patient characteristics, volume increase, postoperative complications and outcomes were analyzed.RESULTS:
The first patient underwent liver transection 16 weeks after failed PVL with a standardized FLR (sFLR) of 30%, which increased to 47% in 7 days. The second patient showed a sFLR of 25% 28 weeks after PVL and subsequent PVE of segment IV, which increased to 41% in 7 days after transection. The third patient underwent liver partition 8 weeks after PVE with a sFLR of 19%, which increased to 37% in six days. All patients underwent a R0 resection.CONCLUSION:
Failed PVE or PVL appears to represent a good indication for the isolated parenchymal liver transection according to the newly developed ALPPS approach.Related: Liver Cancer
Swiss HPB Center, Department of Surgery and Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland.
Nagler A, Rocha V, Labopin M, et al.Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen--a report from the acute leukemia working party of the European group for blood and marrow transplantation.
J Clin Oncol. 2013; 31(28):3549-56 [PubMed
] Related Publications
Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu.PATIENTS AND METHODS:
We performed a retrospective registry-based study comparing outcomes of patients with AML in first or second remission after alloSCT from sibling donors who underwent IV Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning.RESULTS:
Engraftment rate was 98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft-versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year nonrelapse mortality (NRM; ± standard deviation [SD]) was 12% ± 1% in the IV Bu/Cy group and 15% ± 2% in the Cy/TBI group (P = .14), and 2-year relapse incidence (RI; ± SD) was 26% ± 3% and 21% ± 1%, respectively (P = .012). Leukemia-free survival (LFS) rate (± SD) was 61% ± 2% after IV Bu/Cy and 64% ± 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for differences between both groups, patients who received IV Bu/Cy had lower acute and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not statistically different between the two conditioning regimens.CONCLUSION:
This retrospective study shows that final outcomes after myeloablative conditioning using IV Bu/Cy were not statistically different from those after Cy/TBI.Related: Busulfan Cyclophosphamide Acute Myeloid Leukemia (AML)
Arnon Nagler and Avichai Shimoni, Chaim Sheba Medical Center, Tel Hasomer, Israel; Vanderson Rocha, Churchill Hospital, Oxford University Hospitals, Oxford, United Kingdom; Myriam Labopin and Mohamad Mohty, Hôpital Saint-Antoine, Paris University; Gerard Socie, Hôpital St Louis, Paris; Ma...
Sassowsky M, Gut P, Hölscher T, et al.Use of EORTC target definition guidelines for dose-intensified salvage radiation therapy for recurrent prostate cancer: results of the quality assurance program of the randomized trial SAKK 09/10.
Int J Radiat Oncol Biol Phys. 2013; 87(3):534-41 [PubMed
] Related Publications
Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice.METHODS AND MATERIALS:
A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared.RESULTS:
Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different.CONCLUSIONS:
The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.Related: Prostate Cancer
Department of Radiation Oncology and Division of Medical Radiation Physics, Bern University Hospital, Switzerland.
Broemme J, Abu-Isa J, Kottke R, et al.Adjuvant therapy after resection of brain metastases. Frameless image-guided LINAC-based radiosurgery and stereotactic hypofractionated radiotherapy.
Strahlenther Onkol. 2013; 189(9):765-70 [PubMed
] Related Publications
BACKGROUND: Tumor bed stereotactic radiosurgery (SRS) after resection of brain metastases is a new strategy to delay or avoid whole-brain irradiation (WBRT) and its associated toxicities. This retrospective study analyzes results of frameless image-guided linear accelerator (LINAC)-based SRS and stereotactic hypofractionated radiotherapy (SHRT) as adjuvant treatment without WBRT.
MATERIALS AND METHODS: Between March 2009 and February 2012, 44 resection cavities in 42 patients were treated with SRS (23 cavities) or SHRT (21 cavities). All treatments were delivered using a stereotactic LINAC. All cavities were expanded by ≥ 2 mm in all directions to create the clinical target volume (CTV).
RESULTS: The median planning target volume (PTV) for SRS was 11.1 cm(3). The median dose prescribed to the PTV margin for SRS was 17 Gy. Median PTV for SHRT was 22.3 cm(3). The fractionation schemes applied were: 4 fractions of 6 Gy (5 patients), 6 fractions of 4 Gy (6 patients) and 10 fractions of 4 Gy (10 patients). Median follow-up was 9.6 months. Local control (LC) rates after 6 and 12 months were 91 and 77 %, respectively. No statistically significant differences in LC rates between SRS and SHRT treatments were observed. Distant brain control (DBC) rates at 6 and 12 months were 61 and 33 %, respectively. Overall survival (OS) at 6 and 12 months was 87 and 63.5 %, respectively, with a median OS of 15.9 months. One patient treated by SRS showed symptoms of radionecrosis, which was confirmed histologically.
CONCLUSION: Frameless image-guided LINAC-based adjuvant SRS and SHRT are effective and well tolerated local treatment strategies after resection of brain metastases in patients with oligometastatic disease.
Departments of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
Brömme JO, Schmücking M, Arnold A, et al.Taxane-containing induction chemotherapy followed by definitive chemoradiotherapy. Outcome in patients with locally advanced head and neck cancer.
Strahlenther Onkol. 2013; 189(8):618-24 [PubMed
] Related Publications
Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity.MATERIALS AND METHODS:
The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS.RESULTS:
The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively.CONCLUSION:
Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.Related: Head and Neck Cancers
Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland.
von Hohenstaufen KA, Conconi A, de Campos CP, et al.Prognostic impact of monocyte count at presentation in mantle cell lymphoma.
Br J Haematol. 2013; 162(4):465-73 [PubMed
] Related Publications
IOSI - Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Sessa C, Shapiro GI, Bhalla KN, et al.First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors.
Clin Cancer Res. 2013; 19(13):3671-80 [PubMed
] Related Publications
A phase I study was conducted with the primary objective of determining the maximum tolerated dose (MTD) of AUY922 in patients with advanced solid tumors. Secondary objectives included characterization of the safety, pharmacokinetic, and pharmacodynamic profiles. Patients and Methods: Patients with advanced solid tumors received 1-hour i.v. infusions of AUY922 once a week in a 28-day cycle. An adaptive Bayesian logistic regression model that employed observed dose-limiting toxicities (DLT) in the first treatment cycle was used to guide dose-escalation decisions, with the established MTD to be used in phase II studies.RESULTS:
One hundred and one patients were enrolled and explored at doses in the range of 2 to 70 mg/m(2). DLTs occurred in 8 patients (22-70 mg/m(2)) and included diarrhea, asthenia/fatigue, anorexia, atrial flutter, and visual symptoms. At 70 mg/m(2), the AUY922 concentration achieved was consistent with active concentrations in a range of xenograft models. There was evidence of target inhibition in peripheral blood mononuclear cells (HSP70 induction) and tumor (client protein depletion and reduction of metabolic activity by (18)F-FDG PET). The recommended phase II dose (RP2D) of 70 mg/m(2) was proposed on the basis of toxicity and pharmacokinetic and pharmacodynamic profiles.CONCLUSIONS:
At the RP2D of 70 mg/m(2), AUY922 exhibited acceptable tolerability, and phase II single-agent and combination studies have been initiated in patients with HER2-positive breast, gastric, and non-small cell lung cancers.Related: Cancer Prevention and Risk Reduction
Instituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.
Rueegg CS, Gianinazzi ME, Michel G, et al.Do childhood cancer survivors with physical performance limitations reach healthy activity levels?
Pediatr Blood Cancer. 2013; 60(10):1714-20 [PubMed
] Related Publications
The extent to which physical performance limitations affect the ability of childhood cancer survivors to reach healthy activity levels is unknown. Therefore this study aims to describe the effect of different types of limitations on activity levels in survivors.PROCEDURE:
Within the Swiss Childhood Cancer Survivor Study we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2005 aged <16 years. We measured healthy activity levels using international guidelines and assessed different kinds of performance limitations (visual impairment, weight and endurance problems, cardiorespiratory, musculoskeletal, and neurological problems, pain and fatigue syndromes).RESULTS:
The sample included 1,560 survivors (75% response rate), of whom 209 (13.5%) reported they have performance limitations. Forty-two percent of survivors with limitations reached healthy activity levels, compared to 57% of survivors without limitations. Least active were survivors with vision impairments (25% active), weight and endurance problems (27.3%), cardiorespiratory problems (36.4%), and musculoskeletal problems (43.1%). After adjusting for socio-demographic variables and type of cancer, we found that survivors with limitations were 1.4 (95%CI 1.0-2.0; P = 0.047) times more likely to be inactive.CONCLUSIONS:
Although many survivors with physical performance limitations maintain healthy activity levels, there is room for improvement. Adapted and targeted physical activity counseling for survivors with performance limitations might help them to raise level of activity and pursue a healthy lifestyle.Related: Cancer Prevention and Risk Reduction
Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Szucs-Farkas Z, Schick A, Cullmann JL, et al.Comparison of dual-energy subtraction and electronic bone suppression combined with computer-aided detection on chest radiographs: effect on human observers' performance in nodule detection.
AJR Am J Roentgenol. 2013; 200(5):1006-13 [PubMed
] Related Publications
OBJECTIVE: The objective of our study was to compare the effect of dual-energy subtraction and bone suppression software alone and in combination with computer-aided detection (CAD) on the performance of human observers in lung nodule detection.
MATERIALS AND METHODS: One hundred one patients with from one to five lung nodules measuring 5-29 mm and 42 subjects with no nodules were retrospectively selected and randomized. Three independent radiologists marked suspicious-appearing lesions on the original chest radiographs, dual-energy subtraction images, and bone-suppressed images before and after postprocessing with CAD. Marks of the observers and CAD marks were compared with CT as the reference standard. Data were analyzed using nonparametric tests and the jackknife alternative free-response receiver operating characteristic (JAFROC) method.
RESULTS: Using dual-energy subtraction alone (p = 0.0198) or CAD alone (p = 0.0095) improved the detection rate compared with using the original conventional chest radiograph. The combination of bone suppression and CAD provided the highest sensitivity (51.6%) and the original nonenhanced conventional chest radiograph alone provided the lowest (46.9%; p = 0.0049). Dual-energy subtraction and bone suppression provided the same false-positive (p = 0.2702) and true-positive (p = 0.8451) rates. Up to 22.9% of lesions were found only by the CAD program and were missed by the readers. JAFROC showed no difference in the performance between modalities (p = 0.2742-0.5442).
CONCLUSION: Dual-energy subtraction and the electronic bone suppression program used in this study provided similar detection rates for pulmonary nodules. Additionally, CAD alone or combined with bone suppression can significantly improve the sensitivity of human observers for pulmonary nodule detection.
University Hospital and University of Bern, Berne, Switzerland.
Hitz F, Fischer N, Pabst T, et al.Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial.
Ann Hematol. 2013; 92(8):1033-40 [PubMed
] Related Publications
Kantonsspital St. Gallen, St. Gallen, Switzerland.
Forrer F, Oechslin-Oberholzer C, Campana B, et al.Radioimmunotherapy with 177Lu-DOTA-rituximab: final results of a phase I/II Study in 31 patients with relapsing follicular, mantle cell, and other indolent B-cell lymphomas.
J Nucl Med. 2013; 54(7):1045-52 [PubMed
] Related Publications
The aim of this study was to determine the maximum tolerated dose (MTD) and to explore the clinical response to (177)Lu-DOTA-rituximab in the treatment of patients with relapsed follicular, mantle cell, or other indolent lymphomas such as marginal zone lymphoma.METHODS:
To evaluate the MTD, we adjusted the dosage of the radiopharmaceutical according to body surface area (BSA).RESULTS:
The MTD using (177)Lu-DOTA-rituximab was 1,665 MBq/m(2) of BSA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. Significant anemia occurred only at dose level 7 (1,850 MBq/m(2) of BSA). We observed the nadir of platelets after a median of 36 d from treatment and the nadir of granulocytes after a median of 50 d. Median time to recovery to the next lower grade of toxicity was 7 d. Nonhematologic toxicity was negligible. We observed clinical responses at all dose levels and for all lymphoma entities. Some of the responses were durable; the longest follow-up is currently over 8 y. At present, 11 patients are alive and 8 patients are disease-free.CONCLUSION:
Our results demonstrate the safety and feasibility of (177)Lu-DOTA-rituximab treatment for the lymphoma entities tested in this study.Related: Mantle Cell Lymphoma
Institute of Nuclear Medicine, University Hospital Basel, Basel, Switzerland.
Wettstein R, Erba P, Itin P, et al.Treatment of basal cell carcinoma with surgical excision and perilesional interferon-α.
J Plast Reconstr Aesthet Surg. 2013; 66(7):912-6 [PubMed
] Related Publications
The classical treatment of basal cell carcinoma (BCC) is surgical removal. Recent scientific interest has shifted towards alternative, non-surgical interventions in order to decrease the morbidity associated with surgical excision.AIM:
This study aims to evaluate a novel approach that combines surgical excision with perilesional interferon injection in a pilot study.METHOD:
A total of 23 patients with facial nodular/solid BCC were enrolled and randomised to receive surgical removal with frozen-section control followed by a single perilesional infiltration of either interferon-α or Ringer's lactate. Patients were evaluated for signs of local complications and recurrence after a minimal follow-up of 1 year.RESULTS AND CONCLUSION:
No major complications occurred after infiltration of interferon. One patient required oral antibiotics in the interferon group and two patients showed a small wound dehiscence. At the 1-year follow-up, one patient suffered from a recurrence in the control group. No recurrence was observed in the interferon group. A single perilesional infiltration of interferon-α was safe and did not increase the local complication rate. No recurrence was observed. A larger study is required to analyse the potential of this combination approach in order to minimise the safety margin and thereby decrease the morbidity associated with surgery while improving the cure rate.Related: Basal Cell Carcinoma Skin Cancer
Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Basel, Switzerland.
Bontognali S, Pless M, Brutsche MH, et al.Analysis of the EGFR mutation status in head and neck squamous cell carcinoma before treatment with Gefitinib.
Onkologie. 2013; 36(4):161-6 [PubMed
] Related Publications
The efficacy of chemotherapy in metastatic and recurrent squamous cell carcinomas of the head and neck (HNSCC) remains unsatisfactory. Gefitinib offers a new therapeutic option with comparable results and better tolerability than chemotherapy. We conducted this study to see if mutations in the epidermal growth factor receptor (EGFR) might predict the therapeutic benefit in HNSCC patients.PATIENTS AND METHODS:
In a pilot trial, 8 patients with metastatic or recurrent HNSCC were treated palliatively with gefitinib (500 mg/day orally). Forceps biopsies were taken to confirm tumor recurrence and to perform an EGFR mutation analysis.RESULTS:
The EGFR status could be determined in 6 of the 8 patients. 5 patients had no EGFR gene mutation, and 1 patient showed a silent guanine-to-adenosine mutation in position 2607. Even without any relevant mutation in the EGFR, we observed partial remission in 3 of 6 patients treated with gefitinib. We also observed that an additional 4 patients had stable disease for at least 10 weeks. The median progression-free survival was 6.25 months, and the median overall survival was 7.39 months.CONCLUSION:
In HNSCC, there are tumor responses to gefitinib without protein-altering mutations in the EGFR gene.Related: Head and Neck Cancers Gefitinib (Iressa)
Kopf-Hals-Tumor-Zentrum, Universitätsspital Basel, Switzerland.
Mertz KD, Paasinen A, Arnold A, et al.Merkel cell polyomavirus large T antigen is detected in rare cases of nonmelanoma skin cancer.
J Cutan Pathol. 2013; 40(6):543-9 [PubMed
] Related Publications
Studies of Merkel cell polyomavirus (MCPyV) in nonmelanoma skin cancers (NMSC) other than Merkel cell carcinoma (MCC) produced controversial results. Therefore, we studied the prevalence of MCPyV in basal cell carcinoma (BCC) and in squamous cell carcinoma (SCC).METHODS:
Tissue specimens were analyzed for the presence of MCPyV DNA by conventional polymerase chain reaction (PCR). Expression of MCPyV large T protein was determined by immunohistochemistry.RESULTS:
MCPyV DNA was frequently detected in skin cancers by PCR, in 36 of 88 BCCs, in 21 of 75 SCCs and in 10 of 47 normal skin samples. In BCC, a significant difference in the detection rate compared to normal skin was observed. In contrast, weak reactivity for MCPyV large T antigen was detected only sporadically in immunosuppressed patients (2 of 88 BCCs, 1 of 75 SCCs). Mutations of the large T antigen of MCPyV were more frequently observed in MCC than in BCC/SCC.CONCLUSIONS:
Our results suggest that the frequent detection of the MCPyV genome in NMSC by PCR reflects ubiquitous spread of the virus. However, the low immunohistochemical detection rate of MCPyV and the lack of MCC-specific MCPyV mutations argue against an essential role of MCPyV in the development of skin cancers other than MCC.Related: Basal Cell Carcinoma Merkel Cell Polyomavirus Skin Cancer
Institut für Pathologie, Kantonsspital Baselland, Liestal, Switzerland.
Genetti M, Grouiller F, Vulliemoz S, et al.Noninvasive language mapping in patients with epilepsy or brain tumors.
Neurosurgery. 2013; 72(4):555-65; discussion 565 [PubMed
] Related Publications
Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required.OBJECTIVE:
To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery.METHODS:
fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available.RESULTS:
fMRI activations concordant with the anterior and posterior language areas were found in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations.CONCLUSION:
The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical planning of epileptogenic foci and of brain tumors.Related: Childhood Brain Tumours Childhood Brain Tumors
Department of Neurology and Fundamental Neurosciences, Geneva University Hospitals, Geneva, Switzerland.
Gravel P, Samland D, Löffler M, et al.Two innovative pharmaceutical forms of leuprorelin: results from 818 patients with advanced prostate cancer.
Adv Ther. 2013; 30(3):271-85 [PubMed
] Related Publications
This study set out to examine the efficacy and tolerability of two innovative implant forms of leuprorelin acetate in men with advanced hormone-dependent prostate cancer in everyday clinical practice.METHODS:
Data were collected from 818 patients (from 273 centers across Germany) who were pretreated with slow-release luteinizing hormone-releasing hormone (LHRH) agonist formulations and who were about to be switched to the leuprorelin implants. Patients received three injections of 1- or 3-month leuprorelin implant and physicians were asked to complete a case report form specific to each of the three clinic visits. Documented parameters included laboratory measurements, such as testosterone and prostate-specific antigen (PSA) levels, adverse events, and patient- and physician-rated assessments of the therapy.RESULTS:
Compared with baseline, a significant decrease in both testosterone and PSA levels were measured after the first and second injections of leuprorelin implant. These results were confirmed for both the 1-month and 3-month implants in separate analyses. Switching, without treatment interruption, from Trenantone® (Takeda Pharma GmBH, Aachen, Germany) to the leuprorelin implant resulted in a significant decrease in the mean serum testosterone concentrations (P < 0.05) and a nonsignificant increase in the proportion of patients reaching castrate testosterone levels, while the number of patients with PSA values ≤ 4 ng/mL significantly increased (P = 0.045). Similar results were obtained for patients previously treated with goserelin who switched to leuprorelin implant. For 94% of patients, treating physicians rated the efficacy of leuprorelin implant as "very good" or "good." Treatment with leuprorelin implant was well tolerated, with only 61 adverse events reported in 42 (5.1%) patients. Patients and physicians rated the tolerability of leuprorelin implant as "very good" or "good" in 95% and 91% of cases, respectively.CONCLUSIONS:
These results confirm the efficacy, tolerability, and ease of use of the leuprorelin implants among a large population of men with advanced, hormone-dependent prostate cancer treated in a clinical practice setting.Related: Prostate Cancer
Triskel Integrated Services, 4 rue des Terreaux-du-Temple, 1201 Geneva, Switzerland.
Gallerani E, Cathomas R, Sessa C, et al.A phase I study of the oral platinum agent satraplatin in combination with oral vinorelbine in patients with advanced solid malignancies.
Onkologie. 2013; 36(1-2):40-5 [PubMed
] Related Publications
The broad spectrum of antitumor activity of the oral platinum satraplatin (S) and vinorelbine (V) were the rationale for performing a phase I trial to define the maximum tolerated (MTD) and the recommended (RD) dose in adult patients with advanced solid tumors.PATIENTS AND METHODS:
4 dose levels (DLs) of S (mg/m(2)/day, days 1-5) and V (mg/m(2)/day, days 1, 8, 15, and 22) every 28 days were explored: S60/V60 on days 1, 8 and 15 only; S60/V60; S70/V60; and S80/V60. Subsequently, 3 further DLs were evaluated with V omitted on day 22: S70/V60, S80/V60, and S80/V80.RESULTS:
Treating 27 patients, the MTD was S80/V80 on days 1, 8, and 15, with 2 dose-limiting toxicities in 2 patients (nausea and vomiting grade (G) 3 with skipping of V on day 15, and neutropenia G4 with infection). The RD was S80/V60 on days 1, 8, and 15. The most frequent toxicities (any G) were nausea (70%), diarrhea (59%), anorexia (37%), vomiting (33%), asthenia (26%), constipation (26%), and paresthesia (18%). Partial responses were observed in 2 platinum-sensitive ovarian cancer patients and in 1 prostate cancer patient.CONCLUSION:
The combination of S and V is tolerable at a DL of S80/V60 on days 1, 8, and 15; further evaluations in platinum- and V-sensitive tumor types would be of interest.Related: Cancer Prevention and Risk Reduction Vinblastine Satraplatin Vinorelbine
Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.
Neidert MC, Sze L, Zwimpfer C, et al.Soluble α-klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas.
Eur J Endocrinol. 2013; 168(4):575-83 [PubMed
] Related Publications
OBJECTIVE: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery.
DESIGN: Prospective controlled study.
METHODS: We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples.
RESULTS: Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P<0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls.
CONCLUSION: High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).
Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Forrer F, Oechslin-Oberholzer C, Campana B, et al.Is there need for radioimmunotherapy? results of a phase I/II study in patients with indolent B-cell lymphomas using lutetium-177-DOTA-rituximab.
Q J Nucl Med Mol Imaging. 2012; 56(6):544-50 [PubMed
] Related Publications
The aim of the study was to explore the clinical response to 177Lutetium-DOTA-rituximab (177Lu-D-R) and to determine the maximum tolerated dose (MTD) in the treatment of patients with relapsed follicular, mantle cell or other indolent lymphomas such as marginal zone lymphoma as well as to put these results into context with other therapy options for these patients.METHODS:
Treatment consisted of cold rituximab (250 mg/m2) on day 1 and day 8 and 177Lu-DOTA-Rituximab on day 8. Reassessment was done at week 10. Thirty-one patients (males=17, females=14, median number of pretreatments: 3) were treated in seven cohorts. Escalation of injected activity was carried out in steps of 5 mCi/m². Dosimetry was performed in the first 20 patients.RESULTS:
The MTD was found to be 45 mCi/m2. Thrombocytopenia and leukopenia were the dose-limiting toxicities. Significant anemia only occurred at dose level 7. We observed the nadir of platelets after a median of 36 days from treatment with 177Lu-D-R and a nadir of granulocytes after a median of 50 days from 177Lu-D-R treatment. Non-hematological toxicity was negligible. We observed clinical responses at all dose levels and for all lymphoma entities. Some of the responses were durable; the longest follow up in complete remission is currently over eight years.CONCLUSION:
The MTD of 177Lu-DOTA-Rituximab was found to be 45 mCi/m². Non hematologic toxicity was negligible. Responses were seen in all lymphoma entities and at all dose levels tested. Further testing seems to be most promising mainly in follicular and marginal zone lymphoma in particular as the results compare well to other therapy options for these patients with regard to effectiveness, toxicity and discomfort for the patients.Related: Rituximab (Mabthera)
Institute of Nuclear Medicine, University Hospital Basel, Switzerland.
Danuser H, Di Pierro GB, Stucki P, Mattei AExtended pelvic lymphadenectomy and various radical prostatectomy techniques: is pelvic drainage necessary?
BJU Int. 2013; 111(6):963-9 [PubMed
] Related Publications
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The occurence of lymphoceles in patients after radical prostatectomy is well known (2-10%). It appears that patients undergoing open extraperitoneal radical prostatectomy develop more lymphoceles than patients undergoing robot-assisted radical prostatectomy with transperitoneal access. The present study investigates in a prospective randomized manner whether the time of drainage (1 vs 7 days) makes a difference or whether drainage is even necessary. The study data, collected in the same institution, are compared with the incidence of lymphocele in patients treated by robot-assisted radical prostatectomy.OBJECTIVE:
To investigate whether routine drainage is advisable after open extended pelvic lymph node dissection (ePLND) and retropubic radical prostatectomy (RRP) by measuring the incidence of lymphoceles and comparing these results with those of a series of robot-assisted radical prostatectomy (RARP) and ePLND.PATIENTS AND METHODS:
A total of 331 consecutive patients underwent ePLND and RRP or RARP. The first 132 patients underwent open ePLND and RRP and received two pelvic drains; these patients were prospectively randomized into two groups: group 1 (n = 66), in which the drains were shortened on postoperative (PO) days 3 and 5 and removed on PO day 7, and group 2 (n = 66), in which the drains were removed on PO day 1. The next 199 patients were assigned to two consecutive groups not receiving drainage: group 3 (n = 73) undergoing open ePLND and RRP, followed by group 4 (n = 126) treated by transperitoneal robot-assisted ePLND and RARP. All patients had ultrasonographic controls 5 and 10 days and 3 and 12 months after surgery.RESULTS:
Lymphoceles were detected in 6.6% of all patients, 3.3% of whom were asymptomatic and 3.3% of whom were symptomatic. Symptomatic lymphoceles were detected in 0% of group 1, 8% of group 2, 7% of group 3 and 1% of group 4, with groups 2 and 3 differing significantly from group 4 (P < 0.05). In total, 5% of all patients undergoing open RRP (groups 1-3) had symptomatic lymphoceles vs 1% of patients undergoing RARP (group 4) (P = 0.06). Nodal-positive patients had significantly more symptomatic lymphoceles than nodal-negative patients (10% vs 2%) (P < 0.02).CONCLUSIONS:
Symptomatic lymphoceles occur less frequently after open RRP and pelvic drainage over 7 days than after open RRP and pelvic drainage over 1 day or without drainage. Patients undergoing RARP without drainage had significantly fewer lymphoceles than patients receiving open RRP without drainage.Related: Prostate Cancer
Klinik für Urologie, Luzerner Kantonsspital, Luzern, Switzerland.
Viehl CT, Guller U, Langer I, et al.Factors influencing the success of in vivo sentinel lymph node procedure in colon cancer patients: Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer.
World J Surg. 2013; 37(4):873-7 [PubMed
] Related Publications
BACKGROUND: The sentinel lymph node (SLN) procedure has the potential to provide relevant improvement in nodal staging in colon cancer patients. However, there remains room for improvement for SLN identification and sensitivity. Therefore, the objective of the present investigation was to analyze factors influencing the success of the SLN procedure in colon cancer patients.
METHODS: One hundred seventy-four consecutive colon cancer patients were prospectively enrolled in this multicenter study and underwent in vivo SLN procedure with isosulfan blue 1 % followed by open standard oncologic colon resection. Several patient-, tumor-, and procedure-related factors possibly influencing the SLN identification and sensitivity were analyzed.
RESULTS: Sentinel lymph node identification rate and accuracy were 89.1 and 83.9 %, respectively. Successful identification of SLN was significantly associated with the intraoperative visualization of blue lymphatic vessels (p < 0.001) and with female gender (p = 0.024). True positive SLN results were significantly associated with higher numbers of SLN (p = 0.026) and with pN2 stage (p = 0.004). There was a trend toward better sensitivity in patients with lower body mass index (BMI) (p = 0.050).
CONCLUSIONS: The success of the SLN procedure in colon cancer patients depends on both procedure-related factors (intraoperative visualization of blue lymphatic vessels, high number of SLN identified) and patient factors (gender, BMI). While patient factors can not be influenced, intraoperative visualization of blue lymphatics and identification of high numbers of SLN are key for a successful SLN procedure.
Department of Surgery, University Hospital Basel, 4031, Basel, Switzerland.
Zucca E, Conconi A, Laszlo D, et al.Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 Randomized Study.
J Clin Oncol. 2013; 31(5):565-72 [PubMed
] Related Publications
Apart from localized gastric disease, there is no consensus on standard initial treatment of mucosa-associated lymphoid tissue lymphoma. The IELSG-19 study (Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma) was launched to compare chlorambucil alone versus chlorambucil plus rituximab in patients not previously given systemic anticancer therapy.PATIENTS AND METHODS:
Patients not responding to or not suitable for local therapy were eligible. In arm A, chlorambucil was given daily 6 mg/m(2) orally (PO) for 6 weeks. Responding patients and those with stable disease continued to be given daily chlorambucil 6 mg/m(2) PO for 14 consecutive days every 28 days for four cycles. In arm B, intravenous rituximab 375 mg/m(2) per day was added on days 1, 8, 15, 22, 56, 84, 112, and 140. After completion of the planned accrual, the protocol was amended to introduce a third arm with rituximab alone. We report the planned final analysis of the first two arms (113 patients in arm A and 114 in arm B).RESULTS:
At a median follow-up of 62 months, the 5-year event-free survival (EFS) was significantly better for the patients treated in arm B (68% v 50%; P = .002) who, despite similar overall response rates (90% v 87%), achieved a higher complete remission rate (78% v 65%; P = .025). Progression-free survival was also improved but it did not reach statistical significance (P = .057). Five-year overall survival (OS) was 89% in both arms. Both treatments were well tolerated without unexpected toxicities.CONCLUSION:
Both treatments were active; the better response rate and EFS obtained with the addition of rituximab did not translate into improved OS.Related: Chlorambucil MALT Lymphoma Rituximab (Mabthera)
Oncology Institute of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland.
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