Now showing items 1-20 of 8669

    • VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis

      Nicholson, S.; Tovey, H.; Elliott, Tony; Burnett, S. M.; Cruickshank, C.; Bahl, A.; Kirkbride, P.; Mitra, A. V.; Thomson, A. H.; Vasudev, N.; et al. (2021)
      Background: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit. Methods: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m2, given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable. Results: Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression. Conclusions: Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease.
    • Towards harmonizing clinical linear energy transfer (LET) reporting in proton radiotherapy: a European multi-centric study

      Hahn, C.; Ödén, J.; Dasu, A.; Vestergaard, A.; Fuglsang Jensen, M.; Sokol, O.; Pardi, C.; Bourhaleb, F.; Leite, A.; de Marzi, L.; et al. (2021)
      Background: Clinical data suggest that the relative biological effectiveness (RBE) in proton therapy (PT) varies with linear energy transfer (LET). However, LET calculations are neither standardized nor available in clinical routine. Here, the status of LET calculations among European PT institutions and their comparability are assessed. Materials and methods: Eight European PT institutions used suitable treatment planning systems with their center-specific beam model to create treatment plans in a water phantom covering different field arrangements and fulfilling commonly agreed dose objectives. They employed their locally established LET simulation environments and procedures to determine the corresponding LET distributions. Dose distributions D1.1 and DRBE assuming constant and variable RBE, respectively, and LET were compared among the institutions. Inter-center variability was assessed based on dose- and LET-volume-histogram parameters. Results: Treatment plans from six institutions fulfilled all clinical goals and were eligible for common analysis. D1.1 distributions in the target volume were comparable among PT institutions. However, corresponding LET values varied substantially between institutions for all field arrangements, primarily due to differences in LET averaging technique and considered secondary particle spectra. Consequently, DRBE using non-harmonized LET calculations increased inter-center dose variations substantially compared to D1.1 and significantly in mean dose to the target volume of perpendicular and opposing field arrangements (p < 0.05). Harmonizing LET reporting (dose-averaging, all protons, LET to water or to unit density tissue) reduced the inter-center variability in LET to the order of 10-15% within and outside the target volume for all beam arrangements. Consequentially, inter-institutional variability in DRBE decreased to that observed for D1.1. Conclusion: Harmonizing the reported LET among PT centers is feasible and allows for consistent multi-centric analysis and reporting of tumor control and toxicity in view of a variable RBE. It may serve as basis for harmonized variable RBE dose prescription in PT.
    • Sociodemographic and geographical variation in access to systemic anti-cancer therapies for women with advanced breast cancer: a systematic review

      Pearson, Sally Anne; Taylor, Sally; Marsden, A.; O'Reilly, J. D.; Howell, Sacha J; Yorke, Janelle; University of Manchester, England; (2021)
      Background: Equitable access to guideline concordant treatment with systemic anti-cancer therapies (SACT) is a key determinant in overall survival, progression free survival and improvement in quality of life for Advanced Breast Cancer (ABC). Variation in treatment receipt has been reported though remains poorly understood. A comprehensive understanding of factors which influence access and receipt of guideline concordant treatment is lacking. The review sought to address this through identifying and investigating factors associated with access to and receipt of guideline concordant SACT for women with ABC. Methods: Systematic searches of the literature were undertaken using EBSCO CINAHL Plus, Ovid MEDLINE, Ovid EMBASE, PsychINFO, Cochrane Library, JBI database and NHS Evidence. Methodological quality was assessed by two reviewers using the Joanna Briggs Institute critical appraisal tool (JBI, 2017) with the application of an overall GRADE quality rating. Studies were synthesised using a narrative synthesis approach. High levels of heterogeneity between studies precluded meta-analysis. Results: Thirteen international studies (n=13) published between 2009 and 2020 were included and reported 201,677 patients with ABC. Overall receipt of SACT ranged from 4% to 70%, factors associated with receipt were: • Age: younger patients had an increased likelihood of treatment receipt in a timelier manner • Race/ethnicity: patients of white origin were more likely to receive treatment in a timelier manner than patients of non-white origin. • Socioeconomic status: patients with higher socioeconomic status were more likely to receive treatment than their counterparts • Comorbidities: patients with fewer comorbidities were more likely to receive treatment • Place of care: patients treated at teaching, research and private institutions were more likely to receive timelier treatment • Geographical location: treatment receipt varied by geographical location Conclusion: A number of factors were associated with treatment receipt. Barriers included older age, non-white race, lower socioeconomic status, significant comorbidities, hospital setting and geographical location. However, due to limitations in overall methodological quality findings should be interpreted with caution. Implications for nursing, practice and research include the development and piloting of targeted interventions to address specific barriers in a socio-culturally sensitive manner and further research to understand the experience of women and clinicians is required.
    • Pulmonary toxicities associated with the use of immune checkpointiInhibitors: an update from the immuno-oncology subgroup of the neutropenia, infection & myelosuppression study group of the Multinational Association for Supportive Care in Cancer

      Rapoport, B. L.; Shannon, V. R.; Cooksley, Timothy J; Johnson, D. B.; Anderson, L.; Blidner, A. G.; Tintinger, G. R.; Anderson, R.; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa (2021)
      The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, with agents such as nivolumab, pembrolizumab, and cemiplimab targeting programmed cell death protein-1 (PD-1) and durvalumab, avelumab, and atezolizumab targeting PD-ligand 1 (PD-L1). Ipilimumab targets cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). These inhibitors have shown remarkable efficacy in melanoma, lung cancer, urothelial cancer, and a variety of solid tumors, either as single agents or in combination with other anticancer modalities. Additional indications are continuing to evolve. Checkpoint inhibitors are associated with less toxicity when compared to chemotherapy. These agents enhance the antitumor immune response and produce side- effects known as immune-related adverse events (irAEs). Although the incidence of immune checkpoint inhibitor pneumonitis (ICI-Pneumonitis) is relatively low, this complication is likely to cause the delay or cessation of immunotherapy and, in severe cases, may be associated with treatment-related mortality. The primary mechanism of ICI-Pneumonitis remains unclear, but it is believed to be associated with the immune dysregulation caused by ICIs. The development of irAEs may be related to increased T cell activity against cross-antigens expressed in tumor and normal tissues. Treatment with ICIs is associated with an increased number of activated alveolar T cells and reduced activity of the anti-inflammatory Treg phenotype, leading to dysregulation of T cell activity. This review discusses the pathogenesis of alveolar pneumonitis and the incidence, diagnosis, and clinical management of pulmonary toxicity, as well as the pulmonary complications of ICIs, either as monotherapy or in combination with other anticancer modalities, such as thoracic radiotherapy.
    • Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial

      Halabi, S.; Yang, Q.; Carmack, A.; Zhang, S.; Foo, W. C.; Eisen, T.; Stadler, W. M.; Jones, R. J.; Garcia, J. A.; Vaishampayan, U. N.; et al. (2021)
      Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.
    • The analysis of COVID-19 on ICU nurses with solutions to improve wellbeing

      Carter, Nicole; Christie Hospital, Manchester (2021)
      Introduction: To ease the psychological ramifications that COVID-19is having on ICU nurses, it is recommended that implementing aWellbeing Action Tool, would be beneficial in maintaining staffwellbeing and high quality patient care.Literature search: Robbins (2020) and Haskell et al. (2020) concludedthat leaders needed to find a solution to support staff to engage inself care. Glasper (2020) found that the wellbeing of nurses is crucialand support from colleagues is vital for both the nurse and patient; asthe care patients receive is only as good as the nurse deliveringit. Maben et al. (2020) and Yuanyuan-Mo (2020) conclude that earlyintervention from nurses is vital and supporting nurses practically andpsychologically must be made a priority.Findings: Synthesising the evidence, the themes emerged included;adopting an open culture, support of nurses and employing in selfcare.In December 2019, a public health emergency was declared (Purba,2020) with deaths passing 149.968, those being our friends, colleagues and family members and the support of nurses must bemade a priority. It is proposed that implementing an ICU WellbeingAction Tool, would prove beneficial for staff to adopt in selfcare andmaintain an open culture to access support.A survey carried out involving 3.500 ICU nurses found that 9 out of10 thought their mental health had declined.Discussion: It is acknowledged the pandemic isn't just a crisis in ourphysical health, but mental health too and finding a solution short andlong term is essential in maintaining staff health, as well as patientsafety, in order to maintain high-quality patient care on ICU. It sup-ports the evidence that staff must adopt an open culture in accessingsupport and employing self compassion to maintain their ownwellbeing and maintain patient safety.Implications for practice: This tool can be used by managers as a for-mal PDR approach or by yourself to develop one's own awareness ofstress triggers. It is recommended further research of this tool and theevaluation of it would be beneficial with the tool being transferable to other areas.
    • Radial artery access for hepatic chemosaturation: the first description of technical feasibility

      Frost, Joshua | Najran, Pavan; Bell, Jon; Mullan, Damian; Radiology and Interventional Radiology, The Christie NHS Foundation Trust, Manchester (2021)
      Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System, Delcath Systems Inc, Wilmington, Delaware) is an interventional radiology procedure that delivers high doses of melphalan, a chemotherapeutic agent, directly to the liver in patients with unresectable primary and secondary liver tumours. Traditionally, CS-PHP is delivered by arterial access via the femoral artery. However, there can be many risks and adverse effects associated with femoral artery punctures, such as retroperitoneal haemorrhage and haematoma formation. The monitoring and bed rest required following the removal of a femoral arterial catheter may also cause significant distress to patients as they remain immobile, potentially prolonging their stay in hospital. The radial artery is an alternative access point, with fewer reported adverse events and increased patient tolerance when compared with femoral access. This case report details the first reported use of Hepatic CHEMOSAT® therapy being delivered via the radial artery. Two patients received hepatic chemosaturation with no reported complications. This report demonstrates that access via the radial artery is a feasible alternative for the delivery of chemotherapy, which may reduce morbidity and the risks usually associated with femoral access.
    • Pembrolizumab plus platinum-based chemotherapy for squamous non-small cell lung cancer: the new kid on the block

      Hockenhull, Kimberley; Ortega-Franco, Ana; Califano, Raffaele; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK (2021)
    • Prophylactic cranial irradiation (PCI), hippocampal avoidance (HA) whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) in small cell lung cancer (SCLC): Where do we stand?

      Crockett, Cathryn; Belderbos, J.; Levy, A.; McDonald, F.; Le Péchoux, C.; Faivre-Finn, Corinne; Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom (2021)
      Small cell lung cancer (SCLC) is an aggressive form of lung cancer associated with an increased risk of develping brain metastases (BM), which are a significant cause of morbidity and mortality. Prophylactic cranial irradiation (PCI) was first introduced in the 1970s with the aim of reducing BM incidence and improving survival and quality of life (QoL). Prospective clinical trials and meta-analyses have demonstrated its effectiveness in reducing BM incidence and improving survival, across all stages of the disease following response to induction chemotherapy. Despite its long history, "unknowns" surrounding PCI use still exist and there are particular subgroups of patients for which its use remains controversial. PCI is known to cause neurocognitive toxicity which can have a significant impact on a patient's QoL. Strategies to minimise this, including the use of hippocampal avoidance radiotherapy techniques, neuroprotective drugs and stereotactic radiosurgery in place of whole brain radiotherapy for the treatment of BM, are under evaluation. This review offers a summary of the key PCI trials published to date and the current treatment recommendations based on available evidence. It also discusses the key questions being addressed in ongoing clinical trials and highlights others where there is currently a knowledge gap and therefore where further data are urgently required.
    • Prognostic significance and therapeutic implications of Caveolin-1 in gastrointestinal tract malignancies

      Kamposioras, Konstantinos; Vassilakopoulou, M.; Anthoney, A.; Bariuoso, Jorge; Mauri, D.; Mansoor, Was; Papadopoulos, V.; Dimas, K.; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK (2021)
      Caveolin-1 (CAV1) is expressed in several solid tumors both in cancerous cells as well as in tumor stroma and is reported to be related to cancer progression, metastasis, therapy resistance and clinical outcomes. Many studies report contrasting functions of this protein depending on the tumor cell model, the tumor type, or the stage of cancer studied. This protein is reported to function both as tumor suppressor and as tumor promoter. In this review, we aim to summarize translational and clinical studies that provide evidence of the role of CAV1 in tumor progression and survival outcome focusing on tumors of the gastrointestinal (GI) tract. Towards this aim, a detailed search has been performed for studies on the expression and the role of CAV1 in oesophageal, gastric, colorectal, pancreatic cancer and cholangiocarcinoma prognosis. We also review and discuss the implication of CAV1 in the outcome of pharmacological interventions. We conclude that CAV1 has the potential to become an important prognostic, and possibly predictive, biomarker in GI malignancies. It may also become a novel target towards the development of improved cancer therapies. However, it is obvious that there remains a lack of consensus on important issues such as the methodologies and cut-off levels in caveolin assessment. This ultimately result in many studies being contradictory not only in terms of the role of CAV1 as a tumor-promoting or suppressing gene but also in terms of the tumor compartment in which the levels of this protein may be of clinical significance. Addressing these important technical issues, in conjunction with a further elucidation of the role of CAV1 in tumor formation and progression, will delineate the importance of CAV1 in prognostic and therapeutic perspectives.
    • PD-L1 testing and immunotherapy selection - early laboratory experience and its potential role in head and neck cancer management

      Bancu, A.; Cowan, Richard A; Chaturvedi, Anshuman; Department of Histopathology and Molecular Pathology, St James's University Hospital, Leeds, UK (2021)
      Anti-programmed cell death protein-1 (PD-1) therapy has been relatively recently approved in a defined context by NICE in adults in the management of recurrent and metastatic head and neck squamous cell carcinomas (HNSCC). In this context, companion diagnostic programmed cell death ligand-1 (PD-L1) testing, previously established at our center for lung and bladder tumors, was undertaken in a few head and neck cancer cases. The scope of this study was to audit the relevant PD-L1 data and integrate the findings in our current clinical practice, with a view to promote improved routine laboratory biomarkers in HNSCC. Histopathology reports documenting tumor type, PD-L1 result and type of clone/assay were included in this study. Over a 5-year period, PD-L1 testing was undertaken in 199 cancer cases, including 3 with head and neck squamous carcinoma with low focal positive staining. Immunotherapy treatment in HNSCC demonstrates a discreet but still significant improvement in the overall survival of PD-L1 positive subjects.
    • Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation

      Phelan, R.; Im, A.; Hunter, R. L.; Inamoto, Y.; Lupo-Stanghellini, M. T.; Rovo, A.; Badawy, S. M.; Burns, L.; Eissa, H.; Murthy, H. S.; et al. (2021)
      Background: Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Objective: Here, we provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Study design: We utilized systematic review methodology to summarize incidence, risk factors, screening, prevention and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Results: Most of the evidence regarding male GvHD is still based on limited data, precluding strong therapeutic recommendations. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa. Conclusion: Male-specific late effects, probably more under-reported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.
    • Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study

      El Badri, S.; Tahir, B.; Balachandran, K.; Bezecny, P.; Britton, Fiona; Davies, M.; Desouza, K.; Dixon, S.; Hills, D.; Moe, M.; et al. (2021)
      Background: Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years. Methods: 14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities. Results: 276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia. Conclusion: Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.
    • Impact of pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer on health-related quality of life in KEYNOTE-181

      Adenis, A.; Kulkarni, A. S.; Girotto, G. C.; de la Fouchardiere, C.; Senellart, H.; van Laarhoven, H. W. M.; Mansoor, Was; Al-Rajabi, R.; Norquist, J.; Amonkar, M.; et al. (2021)
      Purpose: In the phase III KEYNOTE-181 study (NCT02564263) of patients with advanced esophageal cancer (EC), pembrolizumab monotherapy prolonged overall survival versus chemotherapy as second-line therapy in patients with programmed death ligand 1 combined positive score (CPS) ≥ 10. We present the results of the prespecified health-related quality-of-life (HRQoL) analyses of the squamous cell carcinoma (SCC), CPS ≥ 10, and CPS ≥ 10 SCC populations. Patients and methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC questionnaire (OES18), and EuroQol 5-dimension questionnaire (EQ-5D). Data were analyzed in patients who received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment. Key analyses included baseline to week 9 least squares mean change in global health status/quality of life, functional or symptom subscales, and time to deterioration (≥ 10-point deterioration) for specific subscales. Results: The HRQoL population included 387 patients with SCC. Compliance and completion rates for all three questionnaires were similar in both treatment groups at baseline and week 9. No clinically meaningful differences in global health status/quality of life scores were observed between treatment groups from baseline to week 9 (least squares mean difference, 2.80; 95% CI, -1.48 to 7.08); patients in both treatment groups generally exhibited stable functioning and symptom scores of the QLQ-C30 and QLQ-OES18 from baseline to week 9. Time to deterioration for pain (hazard ratio [HR], 1.22; 95% CI, 0.79 to 1.89), reflux (HR, 2.38; 95% CI, 1.33 to 4.25), and dysphagia (HR, 1.53; 95% CI, 1.02 to 2.31) subscales were similar between treatment groups. These findings were generally similar in the CPS ≥ 10 (n = 218) and CPS ≥ 10 SCC (n = 166) subgroups. Conclusion: In patients with advanced EC, pembrolizumab monotherapy and chemotherapy maintained HRQoL in patients with SCC, CPS ≥ 10, and CPS ≥ 10 SCC.
    • Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia

      Schmid, C.; Labopin, M.; Schaap, N.; Veelken, H.; Brecht, A.; Stadler, M.; Finke, J.; Baron, F.; Collin, M.; Bug, G.; et al. (2021)
      We report on 318 patients with acute leukemia, receiving donor lymphocyte infusion (DLI) in complete hematologic remission (CHR) after allogeneic stem cell transplantation (alloSCT). DLI were applied preemptively (preDLI) for minimal residual disease (MRD, n = 23) or mixed chimerism (MC, n = 169), or as prophylaxis in high-risk patients with complete chimerism and molecular remission (proDLI, n = 126). Median interval from alloSCT to DLI1 was 176 days, median follow-up was 7.0 years. Five-year cumulative relapse incidence (CRI), non-relapse mortality (NRM), leukemia-free and overall survival (LFS/OS) of the entire cohort were 29.1%, 12.7%, 58.2%, and 64.3%. Cumulative incidences of acute graft-versus-host disease (aGvHD) grade II-IV°/chronic GvHD were 11.9%/31%. Nineteen patients (6%) died from DLI-induced GvHD. Age ≥60 years (p = 0.046), advanced stage at transplantation (p = 0.003), shorter interval from transplantation (p = 0.018), and prior aGvHD ≥II° (p = 0.036) were risk factors for DLI-induced GvHD. GvHD did not influence CRI, but was associated with NRM and lower LFS/OS. Efficacy of preDLI was demonstrated by decreasing MRD/increasing blood counts in 71%, and increasing chimerism in 70%. Five-year OS after preDLI for MRD/MC was 51%/68% among responders, and 37% among non-responders. The study describes response and outcome of DLI in CHR and helps to identify candidates without increased risk of severe GvHD.
    • Long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high-risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party-EBMT

      Gutiérrez-García, G.; Martínez, C.; Boumendil, A.; Finel, H.; Malladi, R.; Afanasyev, B.; Tsoulkani, A.; Wilson, K. M. O.; Bloor, Adrian; Nikoloudis, M.; et al. (2021)
      We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.
    • Lymphoma: advances in imaging and radiotherapy - introductory editorial

      Illidge, Timothy M; Mikhaeel, N. G.; Specht, L.; Yahalom, J.; Manchester NIHR Biomedical Research Centre, University of Manchester, Christie Hospital, Manchester (2021)
    • International efforts in geriatric radiation oncology

      Naseer, A.; Cree, A.; Simcock, R.; Jeppesen, S. S.; Morris, L.; Kenis, C.; Hashmi, Amira; Dale, W.; O'Donovan, A.; Applied Radiation Therapy Trinity and Trinity St. James's Cancer Institute, Trinity College Dublin, Ireland (2021)
      Introduction: Geriatric assessment (GA) has been recommended to form part of treatment decision making for older adults with cancer. However despite consensus guidelines from various organizations, GA does not appear to be a part of routine practice in radiation oncology. The aim of the current study was to explore the implementation of GA in radiation oncology. Materials and methods: This anonymous international survey investigated current use of GA in patients presenting for radiation therapy aged 65 years and over, in accordance with Checklist for Reporting Results of Internet E-Surveys (CHERRIES) guidelines. The survey was designed, using Qualitrics™, an online survey tool. It was distributed via SIOG, social media and radiation oncology professional organizations. Survey responses were analyzed using simple descriptive statistics. An additional analysis by creating a dichotomous variable based on awareness of major clinical practice guidelines and current use of GA. Results: Among 158 respondents, there was relatively low awareness of GA guidelines and low uptake of validated tools and processes. A minority of participants, only 16%, stated that they had a specialized geriatric oncology program in their institution. Approximately a third (34%) of respondents were unaware of any GA clinical practice guidelines. With regard to what way participants assess older patients differently to younger patients, 16% reported formally using specific validated tools, whereas 73% reported an informal assessment based on their own judgment, with 5% reporting no difference between younger and older patients. Regarding the use of validated screening tools for geriatric impairments, over half reported using (57%). Regarding GA implementation, the main barriers highlighted included a lack of clinical/support staff, a lack of training, knowledge, understanding or experience about GA and a lack of time. Discussion: Relatively low awareness of guidelines and low uptake of formal GA tools and processes were found. The integration of GA principles into radiation oncology appears to be ad hoc and very much in its infancy. There is a clear need for increased interdisciplinary education and collaboration between the disciplines of radiation oncology and geriatric medicine.
    • Expert consensus on perioperative immunotherapy for local advanced non-small cell lung cancer

      Qiu, B.; Cai, K.; Chen, C.; Chen, J.; Chen, K. N.; Chen, Q. X.; Cheng, C.; Dai, T. Y.; Fan, J.; Fan, Z.; et al. (2021)