Now showing items 41-60 of 11376

    • AIPAC (Active Immunotherapy PAClitaxel): A randomized, double blind, placebo controlled, multinational phase IIb trial evaluating the efficacy of eftilagimod alpha (a soluble LAG-3 fusion protein) in combination with paclitaxel in hormone receptor positive metastatic breast cancer

      Dirix, L; Wildiers, H; Huizing, MT; De Cuypere, E; Schroder, CP; Armstrong, Anne C; Huober, J; Marme, F; Schneeweiss, A; Khan, S; et al. (2020)
      Background: Eftilagimod alpha (efti, previously IMP321) is a recombinant LAG-3Ig fusion protein that binds to MHC class II and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. Efti may lead to the activation of the dendritic cell network and to a strong anti-tumor CD8 T cell response when injected s.c. after chemotherapy at a time when these APC are loaded with tumor antigens. AIPAC (Active Immunotherapy PAClitaxel; NCT02614833) is a Phase IIb trial in hormone receptor (HR)-positive metastatic breast carcinoma patients receiving efti or placebo as adjunctive to weekly paclitaxel as a first-line chemotherapy. The randomized double blinded part (stage 2) has finished recruitment in June 2019. Primary analysis is expected Q1 2020. Methods: This clinical trial is a placebo-controlled, double-blind, 1:1 randomized Phase IIb study aimed to enrol 226 patients at multiple centres across 7 different European countries. Patients with metastatic, HR-positive breast adenocarcinoma receiving first line chemotherapy with weekly paclitaxel and with measurable disease according to RECIST 1.1 are eligible. Patients suitable for Her2/neu targeted therapy are excluded from the trial. In the first treatment phase, paclitaxel (80 mg/m² IV at D1, D8, D15 plus efti (30 mg s.c.) or placebo at D2, D16 will be administered for 6 cycles (1 cycle = 4 weeks). This is followed by a maintenance phase in which stable or responding patients will receive efti or placebo for up to additional 52 weeks (12 injections). The primary endpoint is progression-free survival (PFS) by blinded independent central imaging review. Secondary endpoints include PFS by local assessment, overall survival, tumor response according to RECIST 1.1., time to and duration of response, duration of stable disease and quality of life.
    • Palliative lung radiotherapy: higher dose leads to improved survival?

      Lewis, TS; Kennedy, Jason; Price, Gareth J; Mee, Thomas; Woolf, David K; Bayman, Neil A; Chan, Clara; Coote, Joanna H; Faivre-Finn, Corinne; Harris, Maggie A; et al. (2020)
      Aims: Choosing the optimal palliative lung radiotherapy regimen is challenging. Guidance from The Royal College of Radiologists recommends treatment stratification based on performance status, but evidence suggests that higher radiotherapy doses may be associated with survival benefits. The aim of this study was to investigate the effects of fractionation regimen and additional factors on the survival of palliative lung cancer radiotherapy patients. Materials and methods: A retrospective univariable (n = 925) and multivariable (n = 422) survival analysis of the prognostic significance of baseline patient characteristics and treatment prescription was carried out on patients with non-small cell and small cell lung cancer treated with palliative lung radiotherapy. The covariates investigated included: gender, age, performance status, histology, comorbidities, stage, tumour location, tumour side, smoking status, pack year history, primary radiotherapy technique and fractionation scheme. The overall mortality rate at 30 and 90 days of treatment was calculated. Results: Univariable analysis revealed that performance status (P < 0.001), fractionation scheme (P < 0.001), comorbidities (P = 0.02), small cell histology (P = 0.02), 'lifelong never' smoking status (P = 0.01) and gender (P = 0.06) were associated with survival. Upon multivariable analysis, only better performance status (P = 0.01) and increased dose/fractionation regimens of up to 30 Gy/10 fractions (P < 0.001) were associated with increased survival. Eighty-five (9.2%) and 316 patients (34%) died within 30 and 90 days of treatment, respectively. Conclusion: In this retrospective single-centre analysis of palliative lung radiotherapy, increased total dose (up to and including 30 Gy/10 fractions) was associated with better survival regardless of performance status. Keywords: Lung cancer; outcomes research; palliative care; radiotherapy.
    • In Reply to Gupta et al

      Thomson, David J; Yom, SS; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester and the Division of Cancer Sciences, The University of Manchester, Manchester (2020)
    • Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement

      Guckenberger, M; Belka, C; Bezjak, A; Bradley, J; Daly, ME; DeRuysscher, D; Dziadziuszko, R; Faivre-Finn, Corinne; Flentje, M; Gore, E; et al. (2020)
      Background: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. Methods: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. Results: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. Conclusion: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.
    • Obesity and cancer treatment outcomes: interpreting the complex evidence

      Slawinski, CGV; Barriuso, J; Guo, H; Renehan, Andrew G; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. (2020)
      A wealth of epidemiological evidence, combined with plausible biological mechanisms, present a convincing argument for a causal relationship between excess adiposity, commonly approximated as body mass index (BMI, kg/m2), and incident cancer risk. Beyond this relationship, there are a number of challenges posed in the context of interpreting whether being overweight (BMI 25.0-29.9 kg/m2) or obese (BMI ? 30.0 kg/m2) adversely influences disease progression, cancer mortality and survival. Elevated BMI (? 25.0 kg/m2) may influence treatment selection of, for example, the approach to surgery; the choice of chemotherapy dosing; the inclusion of patients into randomised clinical trials. Furthermore, the technical challenges posed by an elevated BMI may adversely affect surgical outcomes, for example, morbidity (increasing the risk of surgical site infections), reduced lymph node harvest (and subsequent risk of under-staging and under-treatment) and increased risk of margin positivity. Suboptimal chemotherapy dosing, associated with capping chemotherapy in obese patients as an attempt to avoid excess toxicity, might be a driver of poor prognostic outcomes. By contrast, the efficacy of immune checkpoint inhibition may be enhanced in patients who are obese, although in turn, this observation might be due to reverse causality. So, a central research question is whether being overweight or obese adversely affects outcomes either directly through effects of cancer biology or whether adverse outcomes are mediated through indirect pathways. A further dimension to this complex relationship is the obesity paradox, a phenomenon where being overweight or obese is associated with improved survival where the reverse is expected. In this overview, we describe a framework for evaluating methodological problems such as selection bias, confounding and reverse causality, which may contribute to spurious interpretations. Future studies will need to focus on prospective studies with well-considered methodology in order to improve the interpretation of causality. Keywords: Cancer; chemotherapy; immunotherapy; obesity; radiotherapy; surgery.
    • Pancreatic cancer

      Mizrahi, JD; Surana, R; Valle, Juan W; Shroff, RT; Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. (2020)
      Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised. High quality computed tomography with intravenous contrast using a dual phase pancreatic protocol is typically the best method to detect a pancreatic tumour and to determine surgical resectability. Endoscopic ultrasound is an increasingly used complementary staging modality which also allows for diagnostic confirmation when combined with fine needle aspiration. Patients with pancreatic cancer are often divided into one of four categories based on extent of disease: resectable, borderline resectable, locally advanced, and metastatic; patient condition is also an important consideration. Surgical resection represents the only chance for cure, and advancements in adjuvant chemotherapy have improved long-term outcomes in these patients. Systemic chemotherapy combinations including FOLFIRINOX (5-fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel remain the mainstay of treatment for patients with advanced disease. Data on the benefit of PARP inhibition as maintenance therapy in patients with germline BRCA1 or BRACA2 mutations might prove to be a harbinger of advancement in targeted therapy. Additional research efforts are focusing on modulating the pancreatic tumour microenvironment to enhance the efficacy of the immunotherapeutic strategies.
    • Parecoxib for opioid-induced hyperalgesia

      Kellett, Emily; Berman, Richard; Morgan, Helen; Collins, Joanne; Department of Palliative & Supportive Care, The Christie NHS Foundation Trust, Manchester, UK (2020)
      This paper describes the case report of a patient admitted to hospital with severe and complex pain and subacute bowel obstruction, who failed to respond to multiple analgesic regimens including ketamine burst and opioid rotation, and was subsequently successfully managed with a parecoxib infusion. Keywords: cancer; drug administration; pain; supportive care.
    • Therapeutic radiographers at the helm: moving towards radiographer-led mr-guided radiotherapy

      Hales, Rosie; Rodgers, John; Whiteside, Lee; McDaid, Lisa; Berresford, Joe; Budgell, Geoff J; Choudhury, Ananya; Eccles, Cynthia L; Radiotherapy, The Christie NHS Foundation Trust, Manchester, UK. (2020)
      Introduction: Magnetic resonance-guided adaptive radiotherapy (MRgART) has the potential to improve treatment processes and outcomes for a variety of tumour sites; however, it requires significant clinical resources. Magnetic resonance linear accelerator (MR-linac) treatments require a daily multidisciplinary presence for delivery. To facilitate sustainable MRgART models, agreed protocols facilitating therapeutic radiographer (RTT)-led delivery must be developed to establish a service similar to conventional image-guided radiotherapy (IGRT). This work provides a clinical perspective on the implementation of a protocol-driven 'clinician-lite' MRgART workflow at one institution. Methods: To identify knowledge, skills, and competence required at each step in the MRgART workflow, an interdisciplinary informal survey and needs assessment were undertaken to identify additional or enhanced skills required for MRgART, over and above those required for conventional cone-beam computed tomography-based IGRT. The MRgART pathway was critically evaluated by relevant professionals to encourage multidisciplinary input and discussion, allowing an iterative development of the RTT-led workflow. Starting with the simplest online adaptation strategy, consisting of a virtual couch shift and online replanning, clear guidelines were established for the delivery of radical prostate radiotherapy with a reduction in staff numbers present. Results: The MRgART-specific skills identified included MRI safety and screening, MR image acquisition, MRI-based anatomy, multimodality image interpretation and registration, and treatment plan evaluation. These skills were developed in RTTs via tutorials, workshops, focussed self-directed reading, teaching of colleagues, and end-to-end workflow testing. After initial treatments and discussions, roles and responsibilities of the three professional groups (clinicians, RTTs, and physicists) have evolved to achieve a 'clinician-lite' workflow for simple radical prostate treatments. Discussion: Through applying a definitive framework and establishing agreed threshold and action levels for action within anticipated treatment scenarios similar to those in cone-beam computed tomography-based IGRT, we have implemented a 'clinician-lite' workflow for simple adaptive treatments on the MR-linac. The responsibility for online plan evaluation and approval now rests with physicists and RTTs to streamline MRgART. Early evaluation of the framework after treatment of 10 patients has required minimal online clinician input (1.5% of 200 fractions delivered). Conclusion: A 'clinician-lite' prostate treatment workflow has been successfully introduced on the MR-linac at our institution and will serve as a model for other tumour sites, using more complex adaptive strategies. Early indications are that this framework has the potential to improve patient throughput and efficiency. Further identification and validation of roles and responsibilities such as online contouring, and more interactive online planning, will facilitate RTTs to fully lead in the online workflow as adaptive radiotherapy becomes ever more complex. Keywords: MR-guided RT; MR-linac; MRL; MRgART; RTT role expansion; resources.
    • Flattening the curve of prostate cancer progression: accurate detection and safe ablation

      Mitin, T; Choudhury, Ananya; Knight Cancer Institute, Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon. (2020)
    • Novel methodology to investigate the impact of radiation dose to heart sub-structures on overall survival

      McWilliam, Alan; Khalifa, J; Vasquez Osorio, Eliana; Banfill, Kathryn; Abravan, Azadeh; Faivre-Finn, Corinne; van Herk, Marcel; Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK (2020)
      Introduction: For lung cancer patients treated with radiotherapy, dose to the heart is associated with excess mortality. However, it is often not feasible to spare the whole heart. Therefore, our aim is to define cardiac sub-structure(s) and dose thresholds which optimally reduce early mortality. Method: 14 cardiac sub-structures were delineated on 5 template patients with representative anatomies. 1,161 non-small cell lung cancer patients were non-rigidly registered to these 5 template anatomies, mapping their radiotherapy dose. Mean and maximum dose to each sub-structure were extracted and the means evaluated as input to prediction models. The cohort was bootstrapped into two variable reduction techniques: elastic-net LASSO and random forest survival model. Each was optimised to extract variables contributing most to overall survival, model coefficients were evaluated to select these sub-structures. The most important variables, common to both models, were selected and evaluated in multivariable cox-proportional hazard models. A threshold dose was defined and Kaplan-Meier survival curves plotted. Results: 978 patients remained after visual QA of the registration. Ranking the model coefficients across the bootstraps selected the maximum dose to the right atrium, right coronary artery and ascending aorta as the most important factors associated with survival. The maximum dose to the combined cardiac region showed significance in the multivariable model, hazard ratio 1.01Gy-1, p=0.03 after accounting for tumour volume (p<0.001), N-stage (p<0.01) and performance status (p=0.01). The optimal threshold for the maximum dose, equivalent dose in 2Gy fractions, was 23Gy. Kaplan-Meier survival curves showed a significant split, log-rank p=0.008. Conclusion: The max dose to the combined cardiac region encompassing the right atrium, right coronary artery and ascending aorta was found to have the greatest impact on patient survival. A maximum EQD2 dose of 23Gy was identified and should be considered as a dose limit in future studies. Keywords: Lung cancer; Radiotherapy; cardiac toxicity; dose response; survival.
    • Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part II: offline and online plan adaption for interfractional changes

      Bertholet, J; Anastasi, G; Noble, D; Bel, A; van Leeuwen, R; Roggen, T; Duchateau, M; Pilskog, S; Garibaldi, C; Tilly, N; et al. (2020)
      Purpose: The POP-ART RT study aims to determine to what extent and how intrafractional real-time respiratory motion management (RRMM), and plan adaptation for interfractional anatomical changes (ART) are used in clinical practice and to understand barriers to implementation. Here we report on part II: ART using more than one plan per target per treatment course. Materials and methods: A questionnaire on the current practice of ART, wishes for expansion or implementation, and barriers to implementation was distributed worldwide. Four types of ART were discriminated: daily online replanning, online plan library, protocolled offline replanning (all three based on a protocol), and ad-hoc offline replanning. Results: The questionnaire was completed by 177 centres from 40 countries. ART was used by 61% of respondents (31% with protocol) for a median (range) of 3 (1-8) tumour sites. CBCT/MVCT was the main imaging modality except for online daily replanning (11 users) where 10 users used MR. Two thirds of respondents wished to implement ART for a new tumour site; 40% of these had plans to do it in the next 2 years. Human/material resources and technical limitations were the main barriers to further use and implementation. Conclusions: ART was used for a broad range of tumour sites, mainly with ad-hoc offline replanning and for a median of 3 tumour sites. There was a large interest in implementing ART for more tumour sites, mainly limited by human/material resources and technical limitations. Daily online replanning was primarily performed on MR-linacs. Keywords: Adaptive radiotherapy; Image-guided radiotherapy (IGRT); Interfractional motion; MR-guided radiotherapy; Plan library; Plan of the day.
    • ESMO Management and treatment adapted recommendations in the COVID-19 era: Lung cancer

      Passaro, A; Addeo, A; Von Garnier, C; Blackhall, Fiona H; Planchard, D; Felip, E; Dziadziuszko, R; de Marinis, F; Reck, M; Bouchaab, H; et al. (2020)
      The COVID-19 pandemic, characterised by a fast and global spread during the first months of 2020, has prompted the development of a structured set of recommendations for cancer care management, to maintain the highest possible standards. Within this framework, it is crucial to ensure no disruption to essential oncological services and guarantee the optimal care.This is a structured proposal for the management of lung cancer, comprising three levels of priorities, namely: tier 1 (high priority), tier 2 (medium priority) and tier 3 (low priority)-defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale.The manuscript emphasises the impact of the COVID-19 pandemic on lung cancer care and reconsiders all steps from diagnosis, staging and treatment.These recommendations should, therefore, serve as guidance for prioritising the different aspects of cancer care to mitigate the possible negative impact of the COVID-19 pandemic on the management of our patients.As the situation is rapidly evolving, practical actions are required to guarantee the best patients' treatment while protecting and respecting their rights, safety and well-being. In this environment, cancer practitioners have great responsibilities: provide timely, appropriate, compassionate and justified cancer care, while protecting themselves and their patients from being infected with COVID-19. In case of shortages, resources must be distributed fairly. Consequently, the following recommendations can be applied with significant nuances, depending on the time and location for their use, considering variable constraints imposed to the health systems. An exceptional flexibility is required from cancer caregivers. Keywords: COVID19; SARS-CoV-2; lung cancer.
    • Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial

      Makawita, S; G, KA-A; Roychowdhury, S; Sadeghi, S; Borbath, I; Goyal, L; Cohn, A; Lamarca, Angela; Oh, DY; Macarulla, T; et al. (2020)
      Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain FGFR alterations. Infigratinib is an oral FGFR 1-3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic FGFR-altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with FGFR2 translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 ( Keywords: cholangiocarcinoma; fibroblast growth factor receptor inhibitor; infigratinib; targeted therapy.
    • Update: the investigation and management of follicular lymphoma

      McNamara, C; Montoto, S; Eyre, TA; Ardeshna, K; Burton, C; Illidge, Timothy M; Linton, Kim M; Rule, S; Townsend, W; Wong, WL; et al. (2020)
    • Optimizing lung cancer radiation treatment worldwide in COVID-19 outbreak

      Liao, Z; Rivin Del Campo, E; Salem, Ahmed; Pang, Q; Liu, H; Lopez Guerra, JL; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: (2020)
      COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. Meanwhile in Asia, where the disease began, the spread continues, in China it seems for now to have passed its peak. Italy, Spain, France, UK, and the US have been the countries more affected in terms of deaths. The coronavirus is more dangerous to the elderly and those with certain pre-existing medical conditions which is precisely the profile of lung cancer patients. Essential cancer services should be delivered but all steps should be taken to protect patients and the health workforce from infection with COVID-19. This presents a major challenge to radiotherapy (RT) departments worldwide. An international panel with expertise in the management of lung cancer in high-volume comprehensive centres has come together to share its experience on COVID-19 preparedness to deliver optimal care in such exceptional circumstances. A comprehensive systematic review of the literature through a PubMed search was undertaken. Twelve recommendations including, among others, the consideration of shorter courses, delays, and the omission of RT for lung cancer are proposed by the panel. In summary, we recommend the screening of every single person accessing the treatment room, the consideration of hypofractionation and to delay postoperative RT for non-small cell lung cancer, to avoid twice-daily treatments and delay or deliver prophylactic cranial irradiation during radio(chemo)therapy for limited-stage small cell lung cancer, review image guided RT images for suspicious image findings, and the use of single-fraction RT for the palliative treatment of stage IV lung cancer patients. Given that lung cancer is one of the most common and severe pathologies in radiation oncology departments, the following recommendations require particularly urgent consideration. The decision-making paths strongly depend on locally available resources, and a tailored approach should be used to attend lung cancer patients during this pandemic. Keywords: COVID-19; Lung cancer; Outbreak; Pandemic; Radiation therapy.
    • Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part I: intra-fraction breathing motion management

      Anastasi, G; Bertholet, J; Poulsen, P; Roggen, T; Garibaldi, C; Tilly, N; Booth, JT; Oelfke, U; Heijmen, B; Aznar, Marianne Camille; et al. (2020)
      Purpose: The POP-ART RT study aims to determine to what extent and how intra-fractional real-time respiratory motion management (RRMM) and plan adaptation for inter-fractional anatomical changes (ART), are used in clinical practice and to understand barriers to implementation. Here we report on part I: RRMM. Material and methods: A questionnaire was distributed worldwide to assess current clinical practice, wishes for expansion or new implementation and barriers to implementation. RRMM was defined as inspiration/expiration gating in free-breathing or breath-hold, or tracking where the target and the beam are continuously realigned. Results: The questionnaire was completed by 200 centres from 41 countries. RRMM was used by 68% of respondents ('users') for a median (range) of 2 (1-6) tumour sites. Eighty-one percent of users applied inspiration breath-hold in at least one tumour site (breast: 96%). External marker was used to guide RRMM by 61% of users. KV/MV imaging was frequently used for liver and pancreas (with fiducials) and for lung (with or without fiducials). Tracking was mainly performed on robotic linacs with hybrid internal-external monitoring. For breast and lung, approximately 75% of respondents used or wished to implement RRMM, which was lower for liver (44%) and pancreas (27%). Seventy-one percent of respondents wished to implement RRMM for a new tumour site. Main barriers were human/financial resources and capacity on the machine. Conclusion: Sixty-eight percent of respondents used RRMM and 71% wished to implement RRMM for a new tumour site. The main barriers to implementation were human/financial resources and capacity on treatment machines. Keywords: Breath hold; Gating; Intra-fractional motion; Real-time respiratory motion management; Tumour tracking.
    • Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer

      Hanna, GJ; Guenette, JP; Chau, NG; Sayehli, CM; Wilhelm, C; Metcalf, Robert; Wong, DJ; Brose, M; Razaq, M; Perez-Ruiz, E; et al. (2020)
      Background: To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M SGC. Methods: The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019. The median follow-up was 22 months (range, 6-55 months). Subjects with HRAS-mutant R/M SGC (any histology) and disease progression within the last 6 months were enrolled. Tipifarnib was dosed orally twice daily. The authors determined the objective response rate using Response Evaluation Criteria in Solid Tumors (version 1.1), duration of response, and molecular predictors of response. Results: A total of 13 patients with R/M SGC were enrolled; all had received prior systemic therapy (1-3 regimens). One objective response was observed; an additional 7 of 12 evaluable patients (58%) had stable disease as their best response with a median duration of 9 months (range, 3-14 months). Five of 7 patients had >10% tumor regression and 6 of 7 had stable disease lasting >6 months. Q61R was the most frequent activating HRAS mutation noted (7 of 13 patients; 54%), but gene variant and allele frequency did not correlate with outcomes. The median progression-free survival was 7 months (95% confidence interval, 5.9-10.1 months), and the median overall survival was 18 months (95% confidence interval, 9.6-22.4 months) with approximately 58.6% of patients alive at 1 year. Survival was similar regardless of HRAS mutant variant or co-occurring PIK3CA alterations. No participant discontinued treatment because of toxicity. Conclusions: Tipifarnib resulted in modest clinical activity with a promising disease control rate among patients with HRAS-mutant, R/M SGC who developed disease progression within the last 6 months. Keywords: HRAS; rare cancers; salivary cancer; targeted therapy; tipifarnib.
    • Reaching out beyond first-line treatments in advanced biliary tract cancers

      Lamarca, Angela; Valle, Juan W; Department of Medical Oncology, The Christie NHS Foundation Trust; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. (2020)
    • Cancer and cardiovascular disease

      Alam, N; Wright, AK; Ashcroft, DM; Renehan, Andrew G; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. (2020)
    • Should we be imaging lymph nodes at initial diagnosis of early-stage mycosis fungoides? Results from the PROCLIPI international Study

      Hodak, E; Sherman, S; Papadavid, E; Bagot, M; Querfeld, C; Quaglino, P; Prince, HM; Ortiz-Romero, PL; Stadler, R; Knobler, R; et al. (2020)
      Background: Early-stage mycosis fungoides (MF) includes patients with dermatopathic lymph nodes (LNs) or early lymphomatous LN involvement. There is lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs. Methods: Review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective International Cutaneous Lymphoma Prognostic Index (PROCLIPI) data. Results: PROCLIPI enrolled 375 patients with T1/T2 MF: 304 classical-MF and 71 folliculotropic-MF. Imaging was performed in 169 patients (45%; 83=CT, 18=PET/CT, 68=U/S); only 9 (5%) had palpable enlarged (?15mm) LNs, with an over-representation of plaques, irrespective of the 10% body-surface-area cutoff which distinguishes T1 from T2. Folliculotropic-MF was not more frequently imaged than classical-MF. Radiologically enlarged LNs (?15mm) were detected in 30 patients (18%); only 7 had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (7/169) to at least IIA, whereas non-selective imaging upstaged another 14% (24/169). LN biopsy, performed in 8/30, identified N3 (extensive lymphomatous involvement) in 2, and N1 (dermatopathic changes) in 6. Conclusion: Physical examination was a poor determinant of LN enlargement/involvement. Presence of plaques was associated with significant increase in identification of enlarged/involved LN in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases detection rate of stage-IIA, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2.