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1.
Cancers (Basel) ; 16(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39001380

ABSTRACT

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

2.
N Engl J Med ; 389(4): 322-334, 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37272534

ABSTRACT

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).


Subject(s)
Rectal Neoplasms , Adult , Humans , Anal Canal/surgery , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Disease-Free Survival , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Leucovorin/administration & dosage , Leucovorin/adverse effects , Neoadjuvant Therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Staging , Organ Sparing Treatments , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Preoperative Care , Preoperative Period
3.
Eur J Cancer ; 183: 11-23, 2023 04.
Article in English | MEDLINE | ID: mdl-36791667

ABSTRACT

BACKGROUND: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients. METHODS: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed. RESULTS: In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7-78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5-91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4-70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5-98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7-51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1-90.6; p < 0.0001). CONCLUSIONS: This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.


Subject(s)
Sarcoma, Small Cell , Sarcoma , Soft Tissue Neoplasms , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Humans , Male , Middle Aged , Young Adult , Biomarkers, Tumor/genetics , Cyclin B , Oncogene Proteins, Fusion , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Retrospective Studies , Sarcoma/genetics , Sarcoma/therapy , Sarcoma/pathology , Sarcoma, Small Cell/genetics , Sarcoma, Small Cell/therapy , Sarcoma, Small Cell/diagnosis , Soft Tissue Neoplasms/pathology
4.
Cancers (Basel) ; 13(17)2021 Sep 06.
Article in English | MEDLINE | ID: mdl-34503292

ABSTRACT

Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team.

5.
Case Rep Surg ; 2021: 8811155, 2021.
Article in English | MEDLINE | ID: mdl-33564486

ABSTRACT

BACKGROUND: Neuroendocrine tumors (NETs) are a rare entity and are most commonly found in the gastroenteropancreatic tract. The clinical outcome depends on the potential resectability, grade, and stage. Here, we report a case of a tumor debulking in a metastatic NET of the pancreas. A 25-year-old woman with stable metastatic NET of the pancreas G2 T4N1M1 (hepatic, extrahepatic) already underwent several therapies. Case Presentation. A 25-year-old woman with stable metastatic NET of the pancreas G2 T4N1M1 (hepatic, extrahepatic) already underwent several pharmaceutical therapies. Due to the young age, the G2 characteristic, and the stable liver disease, the decision for debulking was made. Based on a 3D CT scan, an embolization was successfully performed directly prior to a pylorus-preserving pancreatic head resection, advanced interaortocaval lymph node dissection, and an atypical liver resection within segment VI. Histological workup revealed a stage pT3, G2, pN1 (29/34), pM1c (hepatic and extrahepatic), L1, V0, Pn0 with complete surgical resection of the primary tumor (180 mm). The excision of the liver segment V showed a completely resected metastasis. CONCLUSIONS: In this patient, extensive surgery of a pancreatic NET with the aim of a prolonged progression-free survival was performed. Close cooperation between different disciplines is absolutely mandatory. Modern imaging allowed a precise therapy plan to be worked out.

6.
Nat Med ; 27(2): 289-300, 2021 02.
Article in English | MEDLINE | ID: mdl-33495604

ABSTRACT

Synovial sarcoma (SyS) is an aggressive neoplasm driven by the SS18-SSX fusion, and is characterized by low T cell infiltration. Here, we studied the cancer-immune interplay in SyS using an integrative approach that combines single-cell RNA sequencing (scRNA-seq), spatial profiling and genetic and pharmacological perturbations. scRNA-seq of 16,872 cells from 12 human SyS tumors uncovered a malignant subpopulation that marks immune-deprived niches in situ and is predictive of poor clinical outcomes in two independent cohorts. Functional analyses revealed that this malignant cell state is controlled by the SS18-SSX fusion, is repressed by cytokines secreted by macrophages and T cells, and can be synergistically targeted with a combination of HDAC and CDK4/CDK6 inhibitors. This drug combination enhanced malignant-cell immunogenicity in SyS models, leading to induced T cell reactivity and T cell-mediated killing. Our study provides a blueprint for investigating heterogeneity in fusion-driven malignancies and demonstrates an interplay between immune evasion and oncogenic processes that can be co-targeted in SyS and potentially in other malignancies.


Subject(s)
Carcinogenesis/genetics , Molecular Targeted Therapy , Oncogene Proteins, Fusion/genetics , Sarcoma, Synovial/drug therapy , Cell Line, Tumor , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases/genetics , Histone Deacetylases/therapeutic use , Humans , Oncogene Proteins, Fusion/antagonists & inhibitors , Oncogenes/genetics , RNA-Seq , Sarcoma, Synovial/genetics , Sarcoma, Synovial/pathology , Single-Cell Analysis
7.
J Surg Oncol ; 123(2): 497-504, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33146425

ABSTRACT

BACKGROUND: Chordoma is a rare malignant tumor of the axial skeleton. Percutaneous cryoablation (PCA) is a minimally invasive technique that allows freezing of tumors under imaging control. The purpose of our retrospective study was to investigate the outcome of PCA in a selected cohort of patients with sacrococcygeal chordoma, with a minimum of 5 years follow-up. MATERIALS AND METHODS: Four patients were treated in 10 sessions. The mean follow-up was 57.3 months. We evaluated the feasibility, the procedure-related complications, the impact on pain control and oncological outcomes. RESULTS: Freezing of 100% of the tumor volume was possible in 60%. Pain control was not reliably evaluable. Local recurrence occurred in 90% of the treated lesions; the mean time to progression was 8.1 months (range 1.5-16). At last follow-up, one patient had died of the disease, one of another cause and one was receiving the best supportive care. The only patient alive without the disease had received additional carbon-ion radiotherapy. The 5-year survival rate after index PCA was 50%. CONCLUSION: Complete freezing of the tumor was technically challenging, mainly due to the complex local anatomy. Recurrence occurred in 90% of the lesions treated. PCA should be considered with caution in the curative management of sacrococcygeal chordoma.


Subject(s)
Chordoma/mortality , Cryosurgery/mortality , Neoplasm Recurrence, Local/mortality , Patient Selection , Sacrococcygeal Region/surgery , Adult , Aged , Chordoma/pathology , Chordoma/surgery , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies , Sacrococcygeal Region/pathology , Survival Rate
8.
Eur Radiol ; 31(2): 992-1001, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32851447

ABSTRACT

OBJECTIVES: To perform a correlation analysis between histopathology and imaging in patients with previously untreated pancreatic ductal adenocarcinoma (PDAC) and to determine the prognostic values of clinical, histological, and imaging parameters regarding overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). METHODS: This single-centre study prospectively included 61 patients (32 males; median age, 68.0 years [IQR, 63.0-75.0 years]) with histologically confirmed PDAC and following surgical resection who preoperatively underwent 18F-FDG PET/CT and DW-MRI. On whole lesions, we measured, using a 42% SUVmax threshold volume of interest (VOI), the following quantitative parameters: mean and maximum standardised uptake values (SUVmean and SUVmax), total lesion glycolysis (TLG), metabolic tumour volume (MTV), mean and minimum apparent diffusion coefficient (ADCmean and ADCmin), diffusion total volume (DTV), and MTV/ADCmin ratio. Spearman's correlation analysis was performed to assess relationships between these markers and histopathological findings from surgical specimens (stage; grade; resection quality; and vascular, perineural, and lymphatic invasion). Kaplan-Meier and Cox hazard ratio methods were used to evaluate the impacts of imaging parameters on OS (n = 41), DSS (n = 36), and PFS (n = 41). RESULTS: Inverse correlations between ADCmin and SUVmax (rho = - 0.34; p = 0.0071), and between SUVmean and ADCmean (rho = - 0.29; p = 0.026) were identified. ADCmin was inversely correlated with tumour grade (rho = - 0.40; p = 0.0015). MTV was an independent predictive factor for OS and DSS, while DTV was an independent predictive factor for PFS. CONCLUSION: In previously untreated PDAC, ADC and SUV values are correlated. Combining PET-MRI metrics may help predict PDAC grade and patients' survival. KEY POINTS: • Minimum apparent diffusion coefficient derived from DW-MRI inversely correlates with tumour grade in pancreatic ductal adenocarcinoma. • In pancreatic ductal adenocarcinoma, metabolic tumour volume has been confirmed as a predictive factor for patients' overall survival and disease-specific survival. • Combining PET and MRI metrics may help predict grade and patients' survival in pancreatic ductal adenocarcinoma.


Subject(s)
Pancreatic Neoplasms , Positron Emission Tomography Computed Tomography , Aged , Diffusion Magnetic Resonance Imaging , Fluorodeoxyglucose F18 , Humans , Magnetic Resonance Imaging , Male , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Positron-Emission Tomography , Prognosis , Radiopharmaceuticals , Retrospective Studies
9.
Swiss Med Wkly ; 150: w20375, 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-33232506

ABSTRACT

Fluoropyrimidines (FPs), mainly 5-fluorouracil (5-FU) and its oral prodrug capecitabine (Cap), remain the backbone of the treatment of many different solid tumors. Despite their broad use in clinical routine, 10–40% of patients experience severe, and in rare cases (0.2–0.5%) even lethal, FP-related toxicity in early chemotherapy cycles. Today, there is a plethora of evidence that genetic variants in the gene encoding for the 5-FU catabolising enzyme dihydropyrimidine dehydrogenase (DPD, encoded by DPYD) are predictive of severe FP-related toxicities, and international clinical practice recommendations for DPYD genotype-guided FP dosing and therapeutic drug monitoring (TDM) are available. In spite of this strong evidence and DPYD genotyping becoming standard practice in other countries, it is has not been widely adopted in Switzerland to date. Here, we discuss current guidelines on genotype-guided FP dosing and TDM, and propose recommendations tailored to the situation in Switzerland to facilitate their clinical uptake for the further individualisation of FP chemotherapy. We recommend preemptive testing of four DPYD variants (c.1905+1G>A (rs3918290), c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182, c.1236G>A/HapB3)) in patients with an indication for FP-based chemotherapy, with the costs reimbursed through the compulsory health insurance in Switzerland. Carriers of these variants (6.5% in the Swiss population) have a 40–50% risk of developing severe early-onset toxicity when treated with standard FP doses. In these patients, we therefore recommend the use of a reduced starting dose, based on a dose adjustment scheme provided herein. Furthermore, we recommend the use of infusional 5-FU in patients with a DPYD risk genotype in order to enable TDM-based dose escalation. Only if the use of an infusional 5-FU regimen is not feasible should a slow titration of Cap, starting with the recommended reduced dose and basing further doses on monitoring of toxicity, be considered. Given that several studies have shown that TDM in 5-FU treatment improves not only the therapy’s safety, but potentially also its efficacy, we also include detailed TDM-based dosing guidelines and discuss the pre-analytical aspects of 5-FU TDM.


Subject(s)
Dihydrouracil Dehydrogenase (NADP) , Pharmacogenetics , Dihydrouracil Dehydrogenase (NADP)/genetics , Drug Monitoring , Genotype , Humans , Switzerland
11.
BMC Surg ; 20(1): 78, 2020 Apr 19.
Article in English | MEDLINE | ID: mdl-32306936

ABSTRACT

BACKGROUND: The reverse treatment of patients with synchronous colorectal liver metastases (CRLM) is a sequential approach with systemic chemotherapy first, followed by liver resection, and finally, primary tumor resection. The aim of this study was to assess the feasibility, the radiological and pathological tumor response to neoadjuvant therapy, recurrence rates and long-term survival after reverse treatment in a cohort study. METHODS: Data from patients with CRLM who underwent a reverse treatment from August 2008 to October 2016 were extracted from our prospective hepato-biliary database and retrospectively analyzed for response rates and survival outcomes. Radiological tumor response was assessed by RECIST (Response Evaluation Criteria In Solid Tumor) criteria and pathological response according to TRG (Tumor Regression Grade). Disease-free and overall survival were estimated with Kaplan-Meier survival curves. RESULTS: There were 44 patients with 19 rectal and 25 colonic tumors. The reverse treatment was fully completed until primary tumor resection in 41 patients (93%). Radiological assessment after chemotherapy showed 61% of complete/partial response. Pathological tumor response was major or partial in 52% of patients (TRG 1-3). Median disease-free survival after primary tumor resection was 10 months (95% CI 5-15 months). Disease-free survival at 3 and 5 years was 25% and 25%, respectively. Median overall survival was 50 months (95% CI 42-58 months). Overall survival at 3 and 5 years was 59% and 39%, respectively. CONCLUSION: The reverse treatment approach was feasible with a high rate of patients with complete treatment sequence and offers promising long-term survival for selected patients with advanced simultaneous colorectal liver metastases.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/therapy , Hepatectomy , Liver Neoplasms/therapy , Adult , Aged , Cohort Studies , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoadjuvant Therapy , Retrospective Studies , Treatment Outcome , Young Adult
12.
Cell Rep ; 30(13): 4567-4583.e5, 2020 03 31.
Article in English | MEDLINE | ID: mdl-32234488

ABSTRACT

Ewing sarcoma (EwS) is associated with poor prognosis despite current multimodal therapy. Targeting of EWS-FLI1, the fusion protein responsible for its pathogenesis, and its principal downstream targets has not yet produced satisfactory therapeutic options, fueling the search for alternative approaches. Here, we show that the oncofetal RNA-binding protein LIN28B regulates the stability of EWS-FLI1 mRNA in ~10% of EwSs. LIN28B depletion in these tumors leads to a decrease in the expression of EWS-FLI1 and its direct transcriptional network, abrogating EwS cell self-renewal and tumorigenicity. Moreover, pharmacological inhibition of LIN28B mimics the effect of LIN28B depletion, suggesting that LIN28B sustains the emergence of a subset of EwS in which it also serves as an effective therapeutic target.


Subject(s)
Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Protein c-fli-1/metabolism , RNA-Binding Protein EWS/metabolism , RNA-Binding Proteins/metabolism , Sarcoma, Ewing/pathology , Animals , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Line, Tumor , Cell Proliferation , Cell Self Renewal , Clone Cells , Gene Expression Regulation, Neoplastic , Humans , Kinetics , Mice , Protein Stability , RNA Stability , RNA-Binding Proteins/genetics , Sarcoma, Ewing/genetics , Spheroids, Cellular/pathology
13.
Eur J Surg Oncol ; 46(5): 898-904, 2020 05.
Article in English | MEDLINE | ID: mdl-32037016

ABSTRACT

BACKGROUND: Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS. AIM: To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS. METHOD: A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared. RESULTS: There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p < 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13). CONCLUSION: Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.


Subject(s)
Health Care Costs/statistics & numerical data , Length of Stay/statistics & numerical data , Sarcoma/surgery , Soft Tissue Neoplasms/surgery , Surgical Procedures, Operative/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Leiomyosarcoma/pathology , Leiomyosarcoma/surgery , Liposarcoma/pathology , Liposarcoma/surgery , Male , Middle Aged , Myxosarcoma/pathology , Myxosarcoma/surgery , Neoplasm Recurrence, Local/epidemiology , Recovery of Function , Retrospective Studies , Sarcoma/pathology , Sarcoma, Synovial/pathology , Sarcoma, Synovial/surgery , Soft Tissue Neoplasms/pathology , Survival Rate , Treatment Outcome , Tumor Burden , Young Adult
14.
Rev Med Suisse ; 16(676-7): 72-77, 2020 Jan 15.
Article in French | MEDLINE | ID: mdl-31961089

ABSTRACT

Driven by highly specialized medicine, research and the quest for personalization of treatments, oncology witnessed substantial advances in 2019. This year numerous treatments have consolidated their importance and broadened their indications. Multiple innovative treatments, currently under study, brought hope for future advances, while biomarkers, such as PD-L1, microsatellite instability (MSI), tumor mutational burden (TMB), BRCA1/2 gene mutations, and homologous recombination deficiency (HRD) allowed better selection and customization of available treatments. This article provides an overview of this year's advances in oncology.


Sous l'égide de la médecine hautement spécialisée, de la personnalisation des traitements et secondée par une recherche énergique, l'oncologie a connu en 2019 des avancées considérables. Cette année, de nombreux traitements ont consolidé leur importance et élargi leurs indications. L'annonce d'une pléthore de traitements novateurs, en étude, est source d'espoir pour l'avenir. Des biomarqueurs simples ou composites, tels que l'expression PD-L1, l'instabilité de microsatellite (MSI), la charge mutationnelle tumorale (TMB), les mutations des gènes BRCA1/2 ou un déficit du mécanisme de la recombinaison homologue des bases (HRD) permettent une meilleure sélection et personnalisation des traitements disponibles. Le but du présent article est de rassembler les avancées oncologiques de l'année.


Subject(s)
Biomarkers, Tumor , Neoplasms , Humans , Mutation , Neoplasms/diagnosis , Neoplasms/therapy
15.
J Cancer Res Clin Oncol ; 145(8): 2167, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31201485

ABSTRACT

The article "Neoadjuvant chemoradiotherapy delivered with helical tomotherapy under daily image guidance for rectal cancer patients: efficacy and safety in a large, multi-institutional series".

16.
J Cancer Res Clin Oncol ; 145(4): 1075-1084, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30830296

ABSTRACT

PURPOSE: Helical tomotherapy (HT) has been recently introduced in the neoadjuvant treatment of locally advanced rectal cancer. Aim of this study is to report the toxicity and local control rates of a large series of locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and HT under daily image guidance followed by surgery. METHODS: Data from 117 locally advanced rectal cancer patients treated at two Swiss Radiotherapy departments were collected and analyzed. Radiotherapy consisted of 45 Gy (1.8 Gy/fraction, 5 fractions/week delivered in 5 weeks) to the regional pelvic lymph nodes. Seventy patients also received a simultaneous integrated boost (SIB) up to 50 Gy to the tumor and involved nodes (2 Gy/fraction, 5 fractions/week delivered in 5 weeks). Chemotherapy consisted of capecitabine 825 mg/m2, twice daily, during the irradiation days. After a median interval of 59 days [95% confidence interval (CI) 53-65 days), all patients underwent surgery. RESULTS: Median follow-up was 45 months (range 4-90 months). The overall rate of acute grade 2-4 toxicity was 18.8% (n = 22). Four patients (3.4%) presented a grade 3 dermatitis (n = 1) or diarrhea (n = 3), and 1 (0.8%) demonstrated grade 4 rectal toxicity. No patients presented with grade ≥ 3 hematologic toxicity. Six patients (5.1%) had late grade 3 gastrointestinal toxicity. The 4-year local control rate was 88.4% (95% CI 87.5-88.5%). CONCLUSIONS: Neoadjuvant chemoradiotherapy delivered with HT under daily image guidance is well tolerated and shows a high 4-year local control rates.


Subject(s)
Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/therapeutic use , Capecitabine/therapeutic use , Chemoradiotherapy, Adjuvant , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Radiotherapy, Image-Guided , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Tomography, X-Ray Computed , Whole Body Imaging
17.
Rev Med Suisse ; 15(N° 632-633): 78-81, 2019 Jan 09.
Article in French | MEDLINE | ID: mdl-30629376

ABSTRACT

The year 2018 has been incredibly prolific regarding novelties. Several studies have given impressive results and offer new anticancer perspectives. Immunotherapy is gaining more and more place defining a new standard of care for different types of cancer. In parallel with a new approach combining immunotherapy and chemotherapy that is emerging, new forms of adoptive immunotherapy are on the path of approval by regulatory authorities. At the decision-making level, a large somatic genetic analysis is becoming dominant, whereas the addition of more specific biomarkers is still needed regarding immunotherapy. This article aims to summarize the significant new developments in oncology for 2018 concerning the five most common cancers and adoptive cellular immunotherapy.


L'année 2018 a été extrêmement prolifique en termes de nouveautés. Plusieurs études ont amené des résultats intéressants et offrent de nouvelles perspectives anticancéreuses. L'immunothérapie prend de plus en plus de place définissant un nouveau standard pour le traitement des différents types de cancer. En parallèle d'une nouvelle approche combinant l'immunothérapie et la chimiothérapie qui voit le jour, des nouvelles formes d'immunothérapie adoptive se situent sur la voie d'approbation par les autorités réglementaires. Sur le plan décisionnel, l'analyse génétique somatique large des tumeurs devient prépondérante, alors que l'addition de biomarqueurs plus spécifiques est encore nécessaire concernant l'immunothérapie. Cet article a pour but de résumer les nouveautés majeures survenues en oncologie pour 2018 concernant les cinq cancers les plus fréquents et l'immunothérapie cellulaire adoptive.


Subject(s)
Immunotherapy , Medical Oncology , Neoplasms , Combined Modality Therapy , Humans , Immunotherapy, Adoptive , Medical Oncology/trends , Neoplasms/therapy
19.
Visc Med ; 34(5): 376-379, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30498705
20.
Chemotherapy ; 63(3): 143-147, 2018.
Article in English | MEDLINE | ID: mdl-29898438

ABSTRACT

AIMS OF THE STUDY: The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches. METHODS: This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d'Oncologie including 101 members of various oncological specialties. Participants' demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals. RESULTS: Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4-7) for ovarian, 5/10 (IQR 3-7) for colorectal, and 3/10 (IQR 1-3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6-10). CONCLUSION: Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities.


Subject(s)
Carcinoma/diagnosis , Oncologists/psychology , Peritoneal Neoplasms/diagnosis , Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Carcinoma/secondary , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Humans , Male , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Stomach Neoplasms/pathology , Surveys and Questionnaires
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