• Curative-intent radiotherapy outcomes in NSCLC patients with severe/very severe COPD & lung fibrosis

      Tang, C.; Price, G.; Mistry, H.; Kennedy, Jason; Pemberton, Laura S; Woolf, David K; Bayman, Neil A; Cobben, David; Chan, Clara; Faivre-Finn, Corinne; et al. (2020)
      Purpose or Objective Management of inoperable non-small cell lung cancer (NSCLC) patients with severe chronic obstructive pulmonary disease (COPD) and lung fibrosis is complex. We investigated outcomes of curative-intent thoracic radiotherapy in these patients. Material and Methods A retrospective real world dataset of 587 NSCLC patients with COPD and 34 with lung fibrosis treated with curativeintent thoracic radiotherapy at The Christie NHS Foundation Trust (Manchester, UK) from January 2015 to December 2016 were analysed. COPD severity was graded using Global Initiative for Chronic Obstructive Lung Disease classification (GOLD I-IV), dependent on forced expiratory volume in 1 second (FEV1). The primary endpoint was overall-survival (OS). The longitudinal use of oxygen therapy and Medical Research Council (MRC) dyspnoea scores were evaluated in a patient subset. Demographic and clinical characteristics, baseline lung function and radiotherapy and dosimetric lung parameters were evaluated for association with OS. Results The characteristics for the whole cohort are shown in table 1. 148 (25%) COPD patients received stereotactic ablative body radiotherapy (SABR). Median OS was 20 months (95% CI: 17-21) for GOLD I (mild COPD; n=194), 19 months (95% CI 17-21) for GOLD II (moderate COPD; n=255) and 20 months for GOLD III/ IV (severe and very severe COPD; n=138) patients, respectively (fig1A). FEV1 and GOLD category did not correlate with OS (p≥0.05). Median OS was significantly shorter for patients with lung fibrosis (12 months, 95% CI: 4-18) compared to patients without lung fibrosis (21 months, 95% CI: 19-23); p<0.001 (fig1B). Treatment type (fractionated radiotherapy worse compared to SABR), larger tumour volume, higher dosimetric lung parameters (mean dose, V20 and V5), advanced tumour stage and squamous histology all correlated with poor OS (p<0.05). MRC dyspnoea scores and oxygen therapy data were available in 21 (62%) and 14 (41%) fibrosis patients and 92 (67%) and 40 (30%) GOLD III/ IV COPD patients, respectively. MRC dyspnoea scores were not significantly different before and after radiotherapy in fibrosis and GOLD III/ IV patients (p≥0.05). Oxygen therapy increased after radiotherapy in GOLD III/ IV patients (n=12 before vs n=28 after) and in fibrosis patients (n=4 before vs n=10 after). NSCLC patients with lung fibrosis have poor OS after curative-intent thoracic radiotherapy. FEV1 and COPD severity scores are not prognosticators and should not be considered absolute contraindications for curative-intent thoracic radiotherapy in NSCLC patients. Prospective studies with functional and quality of life assessments are needed to further refine radiotherapy treatment in these patients.
    • Current and emergent therapy options for advanced squamous-cell lung cancer.

      Socinski, M; Obasaju, C; Gandara, D; Hirsch, F; Bonomi, P; Bunn, P; Kim, E; Langer, C; Natale, R; Novello, S; et al. (2017-11-23)
      Squamous-cell lung cancer (SqCLC) is a distinct histologic subtype of non-small-cell lung cancer (NSCLC) that is challenging to treat due to specific clinicopathologic characteristics, which include older age, advanced disease at diagnosis, co-morbid diseases, and the central location of tumors. These characteristics have a bearing on treatment outcomes in advanced SqCLC, resulting in a median survival approximately 30% shorter than for patients with other NSCLC subtypes. In the context of the specific features of SqCLC, we review challenges of treating SqCLC and the current guideline-recommended treatments for advanced (metastatic) SqCLC in different patient subpopulations. We also evaluate recently approved treatment options, including necitumumab, afatinib, nivolumab, pembrolizumab, and atezolizumab, discuss the survival benefits associated with each agent in the advanced SqCLC population, and propose a treatment algorithm incorporating these agents for this challenging-to-treat disease. Lastly, we review the preliminary clinical evidence for immunotherapy agents in development for advanced NSCLC.
    • The current and future management of malignant ascites.

      Smith, E M; Jayson, Gordon C; Department of Palliative Medicine, Christie Hospital, Withington, Manchester, U.K. (2003-04)
      Malignant ascites occurs in association with a variety of neoplasms. It is a frequent cause of morbidity and presents significant problems for which there are no clear management guidelines. In this article we discuss various modalities which are available including diuretic therapy, paracentesis, peritoneovenous shunts and intraperitoneal chemotherapy. There are no randomized trials of diuretic drugs to assess their efficacy in malignant ascites. Phase II data suggest that they are effective in approximately one-third of patients with malignancy, and their efficacy may be determined by plasma renin/aldosterone concentrations. Paracentesis provides relief in up to 90% of patients; because of varying reports of hypovolaemia, some advocate simultaneous intravenous fluid infusion. Permanent percutaneous drains may prevent the need for repeated paracentesis, although there is potential for infection. A peritoneovenous shunt also prevents the need for repeated paracenteses, whilst maintaining normal serum albumin concentrations. Blockage occurs in 25% of shunts, which are contraindicated in the presence of heavily bloodstained ascites because of the risk of occlusion. The preclinical and clinical experience with anti-angiogenic agents such as the matrix metalloproteinase inhibitors and the VEGF antagonists suggests that these agents may have a role in the treatment of malignant ascites.
    • The current and future role of the medical oncologist in the professional care for cancer patients: a position paper by the European Society for Medical Oncology (ESMO).

      Popescu, R; Schäfer, R; Califano, Raffaele; Eckert, R; Coleman, R; Douillard, J-Y; Cervantes, A; Casali, P; Sessa, C; Van Cutsem, E; et al. (2014-01)
      The number of cancer patients in Europe is rising and significant advances in basic and applied cancer research are making the provision of optimal care more challenging. The concept of cancer as a systemic, highly heterogeneous and complex disease has increased the awareness that quality cancer care should be provided by a multidisciplinary team (MDT) of highly qualified healthcare professionals. Cancer patients also have the right to benefit from medical progress by receiving optimal treatment from adequately trained and highly skilled medical professionals. Built on the highest standards of professional training and continuing medical education, medical oncology is recognised as an independent medical specialty in many European countries. Medical oncology is a core member of the MDT and offers cancer patients a comprehensive and systemic approach to treatment and care, while ensuring evidence-based, safe and cost-effective use of cancer drugs and preserving the quality of life of cancer patients through the entire 'cancer journey'. Medical oncologists are also engaged in clinical and translational research to promote innovation and new therapies and they contribute to cancer diagnosis, prevention and research, making a difference for patients in a dynamic, stimulating professional environment. Medical oncologists play an important role in shaping the future of healthcare through innovation and are also actively involved at the political level to ensure a maximum contribution of the profession to Society and to tackle future challenges. This position paper summarises the multifarious and vital contributions of medical oncology and medical oncologists to today's and tomorrow's professional cancer care.
    • Current and future therapeutic approaches for the treatment of small cell lung cancer.

      Rossi, A; Tay, Rebecca; Chiramel, Jaseela; Prelaj, Arsela; Califano, Raffaele; Division of Medical Oncology, Scientific Institute for Research and Health Care (IRCCS) 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy (2018-05)
      Small-cell lung cancer (SCLC) is a very aggressive disease characterized by a high response rate to first-line chemotherapy, but most patients relapse within 1 year with disappointing results to second-line treatments. Chemotherapy has reached a plateau of effectiveness and new therapeutic strategies are needed to change the natural history of SCLC. Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC. Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results. To date, no targeted drugs have been approved for clinical practice but several novel agents are in an advanced stage of clinical development in SCLC.
    • Current and future use of hematopoietic growth factors in cancer medicine.

      Mughal, Tariq I; CRC Division of Medical Oncology, Christie Hospital & Institute of Cancer Research, University of Manchester School of Medicine, Manchester, UK. tmughal@freenet.co.uk (2004-09)
      Myelosuppression, in particular neutropenia and anemia are serious complications of malignancy and its treatment. Neutropenia can make patients vulnerable to potentially life-threatening infection. It often results in dose reductions and delay of planned chemotherapy, which can have a significant detrimental effect on tumour response and survival. Anemia can be associated with a range of debilitating effects, which can severely impair patients' QOL. In addition, there is some evidence recognizing anemia as a poor prognostic indicator, associated with reduced treatment efficacy. Reduction in the duration and severity of neutropenia and anemia is possible by initiation of appropriate growth factors during the first and subsequent cycles of chemotherapy. New and improved growth factor support with agents such as pegfilgrastim and darbepoetin alfa has the potential to improve the management of chemotherapy-induced neutropenia and anemia further. Thrombopoietin is currently in clinical trials to assess its potential role in the treatment of thrombocytopenia in patients with cancer.
    • Current and new biomarkers for early detection, prognostic stratification, and management of gallbladder cancer patients

      García, P.; Lamarca, Angela; Díaz, J.; Carrera, E.; Roa, J. C.; On Behalf Of The European-Latin American Escalon, C.; Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile. (2020)
      Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.
    • Current and novel therapeutic opportunities for systemic therapy in biliary cancer

      Marin, J. J. G.; Prete, M. G.; Lamarca, Angela; Tavolari, S.; Landa-Magdalena, A.; Brandi, G.; Segatto, O.; Vogel, A.; Macias, R. I. R.; Rodrigues, P. M.; et al. (2020)
      Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.
    • Current concepts in the surgical management of non-melanoma skin cancers

      Kosutic, Damir; Haw, W; Ghura, V; The Christie NHS Foundation Trust, Manchester, UK. (2019)
    • Current knowledge and future research directions in treatment-related second primary malignancies.

      Morton, L; Swerdlow, A; Schaapveld, M; Ramadan, S; Hodgson, D; Radford, John A; van Leeuwen, F (2014)
    • Current management and outcome of pregnancies in women with adrenal insufficiency: experience from a multicenter survey

      Bothou, C.; Anand, G.; Li, D. F.; Kienitz, T.; Seejore, K.; Simeoli, C.; Ebbehoj, A.; Ward, E. G.; Paragliola, R. M.; Ferrigno, R.; et al. (2020)
      Context: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective: Multicenter survey on current clinical approaches in managing AI during pregnancy. Design: Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and patients: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.
    • Current management of limited-stage SCLC and CONVERT trial impact: an EORTC LCG survey

      Levy, A; Hendriks, L; Le Pechoux, C; Falk, Sally; Besse, B; Novello, S; Dingemans, A; Hasan, B; Reck, M; Berghmans, T; et al. (2019)
    • Current management of limited-stage SCLC and CONVERT trial impact: results of the EORTC Lung Cancer Group survey

      Levy, A; Hendriks, LEL; Le, PC; Falk, Sally; Besse, B; Novello, S; Dingemans, A; Hasan, B; Reck, M; Berghmans, T; et al. (2019)
      OBJECTIVES: The CONVERT trial showed that twice-daily (BD) concurrent chemoradiotherapy should continue to be considered the standard of care in localised LS-SCLC. A survey was conducted to assess the impact of the CONVERT trial in clinical practice and to identify any relevant research questions for future trials in this setting. METHODS AND MATERIALS: An EORTC Group online survey of LS-SCLC practice was distributed to the EORTC LCG and to members of several European thoracic oncology societies between April and December 2018. RESULTS: 198 responses were analysed. The majority of respondents (88%, n?=?174) were aware of the CONVERT trial. Radiation oncologists comprised 56% of all respondents. Once-daily (OD) radiotherapy is still the most commonly used regimen, however the use of concurrent BD radiotherapy increased after the publication of CONVERT (n?=?59/186, 32% prior to and n?=?78/187, 42% after the publication, p?=?0.053). The main reasons for not implementing BD after the CONVERT publication were logistical issues (n?=?88, 44%), inconvenience for patients (n?=?56, 28%), and the absence of a statistical survival difference between the two arms in CONVERT (n?=?38, 19%). Brain MRI was used by 28% during staging but more than half (60%) of the respondents did not routinely image the brain during follow-up. The main research questions of interest in LS-SCLC were 1) integrating novel targeted therapies-immunotherapies (n?=?160, 81%), 2) PCI (+/- hippocampal sparing) vs. MRI surveillance (n?=?140, 71%) and, 3) biomarker driven trials (n?=?92, 46%). CONCLUSION: Once daily radiotherapy (60-66?Gy in 30-33 fractions) remains the most prescribed radiotherapy fractionation, despite the findings suggested by the CONVERT trial.
    • Current management practices for acromegaly: an international survey.

      Giustina, A; Bronstein, M D; Casanueva, F F; Chanson, P; Ghigo, E; Ho, K K Y; Klibanski, A; Lamberts, S; Trainer, Peter J; Melmed, S; et al. (2011-06)
      To determine whether peer-reviewed consensus statements have changed clinical practice, we surveyed acromegaly care in specialist centers across the globe, and determined the degree of adherence to published consensus guidelines on acromegaly management. Sixty-five acromegaly experts who participated in the 7th Acromegaly Consensus Workshop in March 2009 responded. Results indicated that the most common referring sources for acromegaly patients were other endocrinologists (in 26% of centers), neurosurgeons (25%) and primary care physicians (21%). In sixty-nine percent of patients, biochemical diagnoses were made by evaluating results of a combination of growth hormone (GH) nadir/basal GH and elevated insulin like growth factor-I (IGF-I) levels. In both Europe and the USA, neurosurgery was the treatment of choice for GH-secreting microadenomas and for macroadenomas with compromised visual function. The most widely used criteria for neurosurgical outcome assessment were combined measurements of IGF-I and GH levels after oral glucose tolerance test (OGTT) 3 months after surgery. Ninety-eight percent of respondents stated that primary treatment with somatostatin receptor ligands (SRLs) was indicated at least sometime during the management of acromegaly patients. In nearly all centers (96%), the use of pegvisomant monotherapy was restricted to patients who had failed to achieve biochemical control with SRL therapy. The observation that most centers followed consensus statement recommendations encourages the future utility of these workshops aimed to create uniform management standards for acromegaly.
    • Current practice for selection of adult patients for proton therapy across Europe

      Tambas, M.; van der Laan, H. P.; Steenbakkers, R.; Doyen, J.; Timmermann, B.; Orlandi, E.; Hoyer, M.; Haustermans, K.; Georg, P.; Burnet, Neil G; et al. (2021)
      Purpose or Objective Among individual proton therapy (PT) centres and European countries, there are major differences regarding patient selection for PT. This is especially true for adult patients who would normally be treated with photon therapy but may benefit from the delivery of PT instead. To obtain insight in the current practice in Europe, we performed a survey on the different selection methods currently applied in the European PT centres. Materials and Methods We first designed electronic questionnaires for eight different tumour sites. The questionnaires consisted of multiple choice, checkbox and open questions regarding the application of PT for adult patients. We focused on four main topics including indications and patient selection methods and criteria, reimbursement, clinical and preclinical on-going or planned studies, and the average number of patients treated with PT per year. Results Links to the online questionnaires were sent to 23 European PT centers of which 19 (83%) participated. Major variability existed regarding the number of tumor types treated with PT (average: 4; range: 1-8) among the participating centres (Figure 1). All centers treated central nervous system tumours (CNS), while tumours of the head and neck cancer (HNC) were treated in 79% , lymphoma in 47%, gastrointestinal in 47%, breast in 32%, prostate in 26%, lung in 26% and gynecological cancers in 11 % of the centers. reimbursement issues (29%), technical limitations (20%), and lack of patient referral (13%). Interestingly, limited treatment capacity was the least reported factor (3%) for not treating a specific tumour type with PT Conclusion Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Interestingly, some countries are more conservative in the number of cancers treated with PT than others. Lack of evidence for PT and reimbursement issues are the most commonly reported reasons for not treating specific tumour types with PT rather than limited treatment capacity.
    • Current practice in proton therapy delivery in adult cancer patients across Europe

      Tambas, M.; Paul van der Laan, H.; R, J. H. M. S.; Doyen, J.; Timmermann, B.; Orlandi, E.; Hoyer, M.; Haustermans, K.; Georg, P.; Burnet, Neil G; et al. (2021)
    • Current practice in the use of cone beam computed tomography: a survey of UK dental practices.

      Yalda, F; Holroyd, J; Islam, M; Theodorakou, Chrysoula; Horner, K; Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PL (2019)
    • Current practice of whole brain radiotherapy in metastatic non-small cell lung cancer.

      Clarke, S; Faivre-Finn, Corinne; Woolf, David K; The University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK (2018-04)
    • Current role of radiotherapy in non-melanoma skin cancer

      Veness, MJ; Delishaj, D; Barnes, EA; Bezugly, A; Rembielak, Agata; Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia (2019)
      Non-melanoma skin cancer (NMSC) represents the most frequently diagnosed malignancy worldwide, most being cutaneous basal cell and squamous cell carcinoma. The global incidence of NMSC continues to increase as the global population ages. Numerous treatment options are available for NMSC patients, with radiotherapy an efficacious and tissue-preserving non-surgical option. External beam radiotherapy and brachytherapy are modalities with specific indications and advantages in treating NMSC. Where excision is not an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic or functional outcome), radiotherapy offers an excellent alternative. Inoperable elderly and/or co-morbid patients of poor performance status can benefit from short-course hypofractionated radiotherapy, with very acceptable toxicity. Adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of local and regional recurrence and associated morbidity and mortality. Radiotherapy has advantages and disadvantages and it is important for clinicians to understand these. Managing patients with NMSC is carried out by clinicians from multiple disciplines but it is imperative that they are all aware of the role of radiotherapy in their patients in various clinical settings. Here we aim to discuss the role and indications for recommending radiotherapy in patients with NMSC.
    • The current role of radiotherapy in the treatment of small cell lung cancer.

      Woolf, David K; Slotman, B; Faivre-Finn, Corinne; The Christie Hospital NHS Foundation Trust, Manchester, UK (2016-08-10)
      Radiotherapy has been shown to play a key role in the management of small cell lung cancer. There are well-established data in the literature for the use of concurrent chemoradiotherapy for stage I-III disease, although key questions remain over the timing of radiation, the optimal dose/fractionation and particularly once versus twice daily treatment, the use of elective nodal irradiation and drug combinations. Data for the use of thoracic radiation in stage IV disease, after chemotherapy, have recently become available and are leading to a change in practice. Prophylactic cranial irradiation has been shown to be of use in both stage I-III and stage IV disease, although uncertainties surround its use in the elderly population and the use of brain imaging before treatment. This overview will address the current available evidence and focus on areas for future research.