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The updated edition of the German, Austrian and Swiss Guidelines for Systemic Treatment of Gastric Cancer was completed in August 2023, incorporating new evidence that emerged after publication of the previous edition. It consists of a text-based "Diagnosis" part and a "Therapy" part including recommendations and treatment algorithms. The treatment part includes a comprehensive description regarding perioperative and palliative systemic therapy for gastric cancer and summarizes recommended standard of care for surgery and endoscopic resection. The guidelines are based on a literature search and evaluation by a multidisciplinary panel of experts nominated by the hematology and oncology scientific societies of the three involved countries.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Áustria , OncologiaRESUMO
BACKGROUND: Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing. METHODS: In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort. RESULTS: In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated. The median number of previous palliative therapy lines was two. The median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI: 1.4-2.8) and 6.3 (95% CI: 3.3-9.3) months, respectively. There was no statistically significant difference in median OS according to microsatellite or PD-L1 status. However, a trend towards prolonged PFS and OS for the microsatellite instability high subgroup could be observed. Patients with an ECOG Performance Status (PS) ≥ 2 displayed a significantly worse outcome than those with an ECOG PS ≤ 1 (p = .03). Only one patient discontinued immunotherapy due to treatment-related toxicity. CONCLUSIONS: Our results support feasibility of nivolumab and pembrolizumab in pre-treated patients with metastatic gastric and GEJ cancer in a Western real-world cohort. Further phase II/III studies are needed to confirm clinical efficacy.
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Neoplasias Esofágicas , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Gástricas , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Áustria , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1-3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m2, cisplatin 75 mg/m2 followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm). RESULTS: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7-12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0-8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1-2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs. CONCLUSION: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs. TRIAL REGISTRATION: Registered at clinicaltrials.gov, NCT01107639, on 21 April 2010.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Esofágicas/terapia , Tromboembolia/epidemiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboembolia/induzido quimicamente , Resultado do TratamentoRESUMO
INTRODUCTION: Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. PATIENTS AND METHODS: The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. RESULTS: Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. CONCLUSION: Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.
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Neoplasias Colorretais/terapia , Terapia por Exercício/métodos , Exercício Físico , Adulto , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Cooperação do Paciente , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline. METHODS: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment. These patients were randomly assigned (1:1) into one of the following four cohorts: liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas. Participants were treated with oral regorafenib (160 mg per day 3 weeks on and 1 week off) or matched placebo. Patients receiving placebo were offered optional crossover in case of centrally confirmed disease progression. The random allocation schedule was computer-generated with permuted blocks of four patients, with two stratification factors: country (France or Austria) and previous exposure to pazopanib (yes or no). Eligibility criteria included patients with histologically proven advanced and inoperable soft tissue sarcomas with intolerance or failure to doxorubicin or other anthracycline-based chemotherapy and at least one unidimensionally or bidimensionally measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The primary endpoint was RECIST-based progression-free survival after central radiological review in the intention-to-treat population. Patients, physicians, and radiologists of the panel were masked to treatment allocation. This study is still open for recruitment for an additional stratum (patients previously treated with pazopanib) and registered with ClinicalTrials.gov, NCT01900743. FINDINGS: From Aug 5, 2013, to Nov 26, 2014, 182 patients were randomly assigned to one of four cohorts and included in the final analysis. At the cutoff date (Jan 7, 2016), the number of required events was reached for the four cohorts. In the liposarcoma cohort, progression-free survival was 1·1 months (95% CI 0·9-2·3) with regorafenib versus 1·7 months (0·9-1·8) with placebo (HR 0·89 [95% CI 0·48-1·64] p=0·70). In the leiomyosarcoma cohort, progression-free survival was 3·7 months (95% CI 2·5-5·0) with regorafenib versus 1·8 (1·0-2·8) months with placebo (HR 0·46 [95% CI 0·46-0·80] p=0·0045). In the synovial sarcoma cohort, progression-free survival was 5·6 months (95% CI 1·4-11·6) with regorafenib versus 1·0 (0·8-1·4) with placebo (HR 0·10 [95% CI 0·03-0·35] p<0·0001). In the other sarcoma cohort, progression-free survival was 2·9 months (95% CI 1·0-7·8) with regorafenib versus 1·0 (0·9-1·9) with placebo (HR 0·46 [95% CI 0·25-0·81] p=0·0061). Before crossover, the most common clinically significant grade 3 or higher adverse events were arterial hypertension (17 [19%] events in the 89 patients in the regorafenib group vs two [2%] events in the 92 patients in the placebo group), hand and foot skin reaction (14 [15%] vs no events) and asthenia (12 [13%] vs six [6%]). One treatment-related death occurred in the regorafenib group due to liver failure. INTERPRETATION: Regorafenib has an important clinical antitumour effect in non-adipocytic soft tissue sarcomas, improving progression-free survival. Regorafenib should be further evaluated in this setting, and its therapeutic role has to be defined in the context of the growing therapeutic armamentarium, already including one approved multikinase inhibitor, pazopanib. FUNDING: Bayer HealthCare.
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Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Sarcoma/mortalidadeRESUMO
PURPOSE: The aim of this study was to analyse the long-term outcome of rectal cancer patients who submitted to preoperative chemoradiation with consecutive intensive follow-up and aggressive surgical treatment of recurrent disease. METHODS: Patients with locally advanced (cT3-4 Nx M0-1) mid/low rectal cancer were treated at a tertiary university hospital with preoperative long-course chemoradiation followed by resection (according to a prospective study protocol). After resection, all patients were urged to participate in a standardised, risk-independent intensive follow-up program. All curatively treated patients (n = 153, 96 %) were included in our long-term analysis with respect to curative re-resection of recurrent disease. RESULTS: Of 153 patients, 143 (93 %) participated in our follow-up program: 63 % were surveyed longer than 5 years after primary therapy (mean follow-up 75 months, 95 % CI 67.8-82.2). Fifty-five (36 %) patients developed cancer recurrence (mean 27.8 months, 95 % CI 20.6-34.9, range 3-108), giving a disease-free survival rate of 68.5 and 60.7 % at 5 and 10 years; 21 (38 %) patients were re-resected curatively and 58 (38 %) patients died during the observation period, giving an overall survival rate of 70.8 and 57.5 % at 5 and 10 years. Multivariate analysis found tumour differentiation (P < 0.01), operative procedure (P < 0.05) and downstaging (P < 0.01) to be independent variables influencing overall survival. CONCLUSIONS: The combination of multimodal therapy and aggressive surgical treatment of metastases including repeated re-resections in curative intention is relevant in order to chronify the disease. Thus, both intensive and extended follow-up beyond 5 years appear to be mandatory.
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Quimiorradioterapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively. In total, 43 patients were enrolled in the ASSO-LM1 trial. Eight patients were ineligible for resection due to protocol violation and progression in two patients. The resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of patients, of which three operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirmed an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS and 5% thromboembolic events. Overall survival significantly differed depending upon the fulfillment of adjuvant treatment in curative resected patients (59.1 mo vs. 30.8 mo). In conclusion, the ASSO-LM1 trial is a hypothesis-generating study confirming the prognostic benefits of perioperative therapy with XELOX and bevacizumab in patients with metastatic colorectal cancer confined to the liver.
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E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.
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PURPOSE: Erythropoiesis-stimulating agents can reduce red blood cell transfusion rates in patients developing anemia while receiving chemotherapy. We investigated potential cost savings from reduced transfusion rates in patients starting darbepoetin alfa (DA) at higher versus lower hemoglobin (Hb) levels. METHODS: Two systematic literature reviews were performed: transfusion outcomes in patients receiving DA stratified by baseline Hb level and costs of transfusion in Europe. Potential cost savings were calculated by multiplying the difference in transfusion rates between Hb levels by the midpoint of transfusion costs. RESULTS: Despite differences in baseline characteristics, treatment duration and analysis technique, the clinical studies (n = 8) showed that fewer transfusions were required when DA was initiated at higher versus lower Hb levels. The economic studies (n = 9) showed that 1 unit of transfusion ranged from
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Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Transfusão de Eritrócitos/economia , Eritropoetina/análogos & derivados , Hemoglobinas/efeitos dos fármacos , Anemia/tratamento farmacológico , Anemia/economia , Antineoplásicos/uso terapêutico , Redução de Custos , Darbepoetina alfa , Transfusão de Eritrócitos/estatística & dados numéricos , Eritropoetina/economia , Eritropoetina/uso terapêutico , Hematínicos/economia , Hematínicos/uso terapêutico , Hemoglobinas/análise , Humanos , PubMedRESUMO
Optimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.
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Assistência ao Convalescente , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Adulto , Áustria , Benzamidas/uso terapêutico , Biópsia , Criança , Terapia Combinada , Comportamento Cooperativo , Diagnóstico Diferencial , Diagnóstico por Imagem , Progressão da Doença , Endoscopia Gastrointestinal , Seguimentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Trato Gastrointestinal/patologia , Trato Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib , Indóis/uso terapêutico , Comunicação Interdisciplinar , Índice Mitótico , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Nomogramas , Cuidados Paliativos , Compostos de Fenilureia/uso terapêutico , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , SunitinibeRESUMO
Over the last decade, therapeutic options for patients with gastric cancer have improved significantly. However, despite these recent advances, mortality is still substantial. Surgery and chemotherapy represent the cornerstones of patient management. Immune checkpoint inhibitors as well as targeted treatments such as HER2-directed therapies and antiangiogenic agents contribute to improved patient prognosis. Herein, we present the updated version of an Austrian consensus on the systemic treatment of patients with gastric adenocarcinoma and adenocarcinoma of the lower gastroesophageal junction, including those with human epidermal growth receptor 2 (HER2) overexpression, microsatellite instability, programmed death-ligand 1 (PD-L1)-positive disease, and claudin 18.2 positivity. The consensus considers the curative setting as well as first-line and later-line systemic treatment options in advanced disease. For HER2-positive disease, HER2 testing is discussed in addition to a review of first-line and later-line therapies. Potential future therapies are also listed, with a focus on targeted [e.g., fibroblast growth factor receptor 2 (FGRF2)-directed] treatments that might provide a further step forward in the management of patients with gastric cancer.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Áustria , Consenso , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Algoritmos , Junção Esofagogástrica/patologia , Receptor ErbB-2/metabolismo , Neoplasias Esofágicas/patologiaRESUMO
Locally advanced or metastatic cholangiocarcinoma is an aggressive carcinoma with a dismal prognosis. For the first-line treatment of locally advanced or metastatic cholangiocarcinoma, cisplatin/gemcitabine has been the standard of care for more than 10 years. Its combination with the immune checkpoint inhibitor durvalumab resulted in an efficiency improvement in the phase III setting. Regarding the use of chemotherapy in the second line, positive phase III data could only be generated for FOLFOX. The evidence base for nanoliposomal irinotecan (Nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) is contradictory. After the failure of first-line treatment, targeted therapies can be offered if the molecular targets microsatellite instability-high (MSI-H), IDH1, FGFR2, BRAF V600E, and NTRK are detected. These targeted agents are generally preferable to second-line chemotherapy. Broad molecular testing should be performed, preferably from tumor tissue, at the initiation of first-line therapy to timely identify potential molecular targets.
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Background: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM. Methods: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS. Results: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively. Conclusions: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.
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Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases.
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Adenocarcinoma , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Adenocarcinoma/patologia , Glândulas Salivares/patologiaRESUMO
BACKGROUND: Recurrent oesophageal cancer after the initial curative multimodality treatment is a disease condition with a poor prognosis. There is limited evidence on recurrence patterns and on the optimal therapeutic approach. METHODS: We analysed the pattern of disease recurrence and subsequent therapies in patients with recurrent oesophageal cancer based on prospectively collected data within a predefined subproject of the randomised phase 3 trial Swiss Group for Clinical Cancer Research (SAKK) 75/08. RESULTS: Among 300 patients included in the SAKK 75/08 trial, tumour recurrence was observed in 103 patients with a median follow-up of 5.8 years. Locoregional recurrence only was found in 26.2% of the patients, 21.4% of patients had both distant and locoregional recurrence and 52.4% of patients had distant recurrence only. Fifty-nine patients (58%) received at least one line of systemic therapy at recurrence, most commonly oxaliplatin-based combination therapies for adenocarcinoma and single-agent chemotherapy for squamous cell carcinoma. Local therapies, most commonly palliative radiotherapy, were used in 49 patients (48%). Six patients underwent a second curative resection or radiochemotherapy. We found no significant overall survival difference for isolated locoregional recurrence versus distant recurrence (15.1 versus 8.7 months, p = 0.167). In a multivariable Cox regression model, time from oesophagectomy to recurrence and the number of recurrence sites as well as the use of systemic therapy or a second curative local therapy significantly correlated with overall survival. CONCLUSIONS: Recurrent oesophageal cancer remains a disease with a poor prognosis and requires multidisciplinary management. A second curative approach for localised disease recurrence may be an option for highly selected patients.
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Neoplasias Esofágicas , Recidiva Local de Neoplasia , Humanos , Seguimentos , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Esofagectomia , QuimiorradioterapiaRESUMO
BACKGROUND/AIM: Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. PATIENTS AND METHODS: Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics. RESULTS: Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. CONCLUSION: Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients.
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Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carbamatos , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , SulfonamidasRESUMO
PURPOSE: In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may lead to higher downstaging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy. PATIENTS AND METHODS: Patients with LARC of the mid and lower rectum, T3NxM0 staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m² twice a day on radiotherapy days; weeks 1-4) and oxaliplatin 50 mg/m² intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level. RESULTS: A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%). CONCLUSIONS: Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT3 LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Capecitabina , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Esquema de Medicação , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Radioterapia Conformacional , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC). However, the clinical evidence of nab-P/G in the elderly (>70 years), who account for the majority of patients with mPC, is limited. This is the first prospective, multicentre, non-interventional study evaluating the tolerability and effectiveness of nab-P/G in younger (≤70 years) versus elderly (>70 years) patients with mPC in the daily clinical routine. METHODS: Eligible patients with mPC were treated with nab-P/G and observed until disease progression or unacceptable toxicity. The primary objectives were safety and tolerability of nab-P/G, and the secondary objectives were efficacy and real-life dosing. RESULTS: A total of 317 patients with mPC (median age, 70 years) were recruited, of which 299, aged ≤70 (n = 162) and >70 (n = 137) years, were eligible for analysis. Baseline characteristics and the safety profile were comparable between the groups. However, fatigue (22.8% versus 13.0%) and decreased appetite (8.8% versus 1.2%) were more frequent in elderly patients. Younger versus elderly patients equally benefited in terms of objective response rate (36% versus 48%), median progression-free survival (5.6 versus 5.5 months; hazard ratio [HR] = 1.03; p = 0.81) and OS (10.6 versus 10.2 months; HR = 0.89; p = 0.4). In addition, the median treatment duration (5 versus 4 cycles), relative dose intensity (70% versus 74%) or reasons for treatment discontinuation were similar. Most patients (56.2% versus 47.4%) benefited from a second-line therapy. CONCLUSION: This prospective real-world analysis confirms the feasibility and tolerability of nab-P/G treatment and reveals OS data similar for younger patients and elderly patients aged >70 years. CLINICALTRIALS. GOV REGISTRATION: NCT02555813. AUSTRIAN NIS REGISTRY: NIS005071.
Assuntos
Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Albuminas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Paclitaxel/farmacologia , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
BACKGROUND: A frequent side effect of the multikinase inhibitor regorafenib is fatigue. Physical activity has shown potential in reducing cancer-related fatigue. METHODS: This non-interventional pilot study assessed physical activity levels of metastatic colorectal cancer (mCRC) patients treated with regorafenib based on median daily step counts measured at 1week intervals using a pedometer. The study further evaluated relations between physical activity levels and fatigue, quality of life (QoL) and progression-free survival. RESULTS: Pedometer data were available for 22 out of 25 enrolled patients. The numbers of days with available pedometer data ranged from 6 to 100 days. The overall median daily step count was 2357 (range 10-14,931), with substantial interindividual and intraindividual variations. Interindividual median weekly step counts were in the range of 5000-7000 in some, 2000-3000 in others, and several hundreds or less in a few patients. Intraindividual daily step counts also varied by several thousands of steps. Step counts in weeks in which patients reported fatigue were well within the range of or even higher than step counts in adjacent weeks, indicating a lack of correlation. The risk of disease progression was also independent of median weekly step counts; however, significant correlations were seen between QoL and step counts. CONCLUSION: Despite the severity of their disease patients showed remarkable levels of walking activity. In view of the highly individual activity levels, exercise prescriptions for seriously ill patient populations should be personalized to the specific needs and preferences of each individual patient.