Now showing items 21-40 of 12617

    • Is robotic surgery safe and feasible for horseshoe kidneys? A multicentre case series

      Ng, A.; Nathan, A.; Campain, N.; Fortune-Ely, M.; Patki, S.; Yuminaga, Y.; Mumtaz, F.; Gulamhusein, Aziz; Tran, M.; Barod, R.; et al. (2021)
      Introduction & Objectives: Horseshoe kidneys (HSK) are the most common renal fusion abnormality. However, they are only present in 0.2% of the population. Due to anatomical variation in vasculature, ectopia and malrotation, surgery has traditionally been performed via an open approach. Robotic surgery has been widely adopted for other urological procedures due to the superior ergonomics; high definition, 3D stereoscopic vision; and 7 degrees of freedom, providing a viable, less invasive surgical option. We aimed to assess the safety and feasibility of robot-assisted surgery for HSK. Materials & Methods: Retrospective data were collected for consecutive patients with HSK undergoing robotic surgery between 2016 and 2020 across two high-volume centres by experienced robotic surgeons. 3D reconstruction using CT renal angiograms were used to help identify vasculature and tumour location, where appropriate. Results: Seven patients underwent robotic surgery for HSK including three partial nephrectomies and one nephroureterectomy for renal masses and three benign nephrectomies for non-functioning kidneys. The median age was 53 years (IQR 44-57) and median BMI was 25 (IQR 25-26.5). Median tumour size in four patients with renal masses was 36 mm (IQR 25-45). Median console time was 120 minutes (IQR 118-215), median operating time was 170 minutes (IQR 155-247) and median estimated blood loss was 150 mL (IQR 125-250). The median pre-operative eGFR was 76 (IQR 72-90) and median post-operative eGFR was 71 (IQR 60-81). There was no grade III or higher Clavien-Dindo complication. There was one Clavien-Dindo II, wound infection complication, requiring a five-day length of stay. All other operations were uneventful and median length of stay was two days. Negative margins were achieved in 75% of tumour resections, and final histology demonstrated clear cell renal cell carcinoma (RCC), RCC, urothelial sarcomatoid and angiomyolipoma. Conclusions: We report one of the largest series of robotic-assisted surgery on HSK. Robotic surgery is safe and feasible for HSK in centralised high centres with acceptable perioperative outcomes, early oncological outcomes and morbidity comparable to standard renal surgery. A further prospective, multi-centre study is required to evaluate the role of robotic surgery in renal fusion anomalies.
    • Treatment-related toxicity using prostate bed versus prostate bed and pelvic lymph node radiation therapy following radical prostatectomy: A national population-based study

      Parry, M. G.; Sujenthiran, A.; Nossiter, J.; Morris, M.; Berry, B.; Cathcart, P.; Clarke, Noel W; Payne, H.; Van der Meulen, J; Aggawal, A.; et al. (2021)
      Introduction & Objectives: There is debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation when used for disease recurrence following radical prostatectomy. This study compared the toxicity of radiation therapy (RT) to the prostate bed and pelvic lymph nodes (PBPLN-RT) with prostate-bed only radiation therapy (PBO-RT). Materials & Methods: Patients with prostate cancer who underwent post-prostatectomy RT in the English National Health Service between 2010-2016 were identified by using data from the Cancer Registry, the National Radiotherapy Dataset, and Hospital Episode Statistics, an administrative database of all hospital admissions. Follow-up was available up to December 31, 2018. Validated indicators were used to identify patients with ≥ Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity according to the presence of both a procedure code and diagnostic code in patient Hospital Episode Statistics records. A competing risks regression analysis, with adjustment for patient and tumour characteristics, estimated subdistribution hazard ratios by comparing GI and GU toxicity for PBPLN-RT vs. PBO-RT. Results: 5-year cumulative incidences in the PBO-RT (n=5,087) and PBPLN-RT (n=593) groups was 18.2% and 15.9% for GI toxicity, respectively. For GU toxicity it was and 19.1% and 20.7%, respectively. There was no difference in GI or GU toxicity between PBO-RT and PBPLN-RT (GI: adjusted sHR, 0.90, 95% CI, 0.67 to 1.19; P=0.45); (GU: adjusted sHR, 1.18, 95% CI, 0.98 to 1.44; P=0.09). Conclusions: Including PLNs in the radiation field following radical prostatectomy is not associated with a significant increase in rates of ≥ Grade 2 GI or GU toxicity at 5 years.
    • Treatment options and outcomes of men with Penile Intraepithelial Neoplasia (PeIN): A systematic review

      Issa, Allaudin; Lee, Esther; Oliveira, Pedro; Lau, Maurice W; Parnham, Arie S; Sangar, Vijay K; Lucky, M.; Grossmann, N.; Fronzaroli, J.; Janisch, F.; et al. (2021)
      Introduction & Objectives: Penile intraepithelial neoplasia (PeIN) is a rare skin condition characterised by dysplastic changes of the epidermal squamous cells which does not extend beyond the basement membrane. Successful treatment options for PeIN with minimal side effects are essential as progression into invasive cancer may require more extensive surgery in a cosmetically sensitive anatomical location. Our aim was to systematically review the published literature for treatment options and outcomes of men with PeIN. Materials & Methods: We performed a systematic review to summarise treatment options and outcomes in the published literature using the electronic databases MEDLINE, EMBASE and Cochrane Database of Systematic Reviews. Results: Of 1594 publications 94 full-text manuscripts of publications were screened and finally 19 studies contributing 691 patients with PeIN were included. Topical therapies included imiquimod and Fluorouracil (5-FU) with complete response rates in 40-100% and 48-74% respectively. Progression after Imiquimod and 5-FU was observed in 20% and 11% respectively. Adverse events were observed in 10% during imiquimod and in 5-12% during 5-FU with the most common being local inflammation causing pain and severe irritation. Phimosis was observed in 5% treated with imiquimod. Discontinuation of treatment in men treated with imiquimod and 5-FU was described in 10% and 11% and one study reported that 11% of men treated with 5-FU were admitted to hospital because of severe inflammation and pain. There were several energy-based therapies discussed in the literature including Yag laser, CO2 laser and phototherapy. Laser treatment demonstrated higher rates of total response (52%-100%). Recurrence was reported in 7%-48%. A significant side effect following laser treatment was a change in penile sensitivity including increased sensitivity in 50% and decrease sensitivity in 15%. Phototherapy led to complete response in 40%-70% but recurrence was observed in 30% and progression in 36%. Surgical treatment of PeIN was associated with recurrence in 4%-30%. Circumcision cleared all preputial PeIN whereas recurrence after surgical treatment of PeIN of the glans was observed in 25% after wide local excision, 4% after Mohs surgery, 5% after total glans resurfacing and 10% after Glansectomy. Conclusions: In summary the data on treatment options and outcomes of men with PeIN is limited and based on small retrospective cohort studies. Our conclusion from the published literature is that circumcision represents the most effective treatment for preputial PeIN whereas several treatment options should be discussed in men with PeIN of the glans and ideally assessed in prospective studies.
    • Perioperative safety and short-term oncological outcomes of minimally invasive retroperitoneal lymph node dissection

      Fankhauser, C D; Afferi, L.; Stroup, S. P.; Rocco, N. R.; Olson, K.; Bagrodia, A.; Cazzaniga, W.; Mayer, E.; Nicol, D.; Islamoglu, E.; et al. (2021)
      Introduction & Objectives: Open Retroperitoneal Lymph Node Dissection (RPLND) is a treatment option in men with stage 1/2 testis cancer and the standard of care in men with post-chemotherapy retroperitoneal residuals. Minimally invasive RPLND (miRPLND) has been introduced but only limited data regarding safety and oncological outcomes are available. Materials & Methods: International, multicentre, retrospective cohort study describing patient characteristics, perioperative safety and oncological outcomes of men scheduled for miRPLND. Results: 406 men (14 sites, 8 countries) were studied. Laparoscopic RPLND was performed in 57 and robotic RPLND in 349 men. Indications included pre-chemotherapy RPLND in 261 including 8 with recurrence after one cycle of adjuvant chemotherapy for stage 1 disease and post-chemotherapy RPLND in 145. The median retroperitoneal mass size was 15mm (IQR 10-19, range 0-31) in pre-chemotherapy RPLND and 20 mm (IQR 15-30, range 0-104) in post-chemotherapy RPLND. Median operative time was 265 minutes (IQR 201-334). Median intraoperative blood loss was 75mL (IQR 50-200) with RBC transfusions in 11 men. Conversion to open surgery was performed in 13 (3%; access problems (6), bleeding complications (4) with blood loss of 1000-6000mL and extent of disease (3)). Intraoperative complications occurred in 15 (4%) men (bleeding (9), ureteric injury (4), bowel injury (1) and thoracic duct injury (1). Postoperative complications in 28 (7%) men included ascites and/or pleural effusion (11), deep vein thrombosis (6), wound infection (3), rhabdomyolysis (2), incisional hernia (2), post-operative bleeding requiring transfusion (1), clostridia difficile infection (1), limb compartment syndrome (1) and pneumonia (1). Median length of stay overall was 3 days (IQR 2-4) and in men with complications 4 days (IQR 2-6). Within the first 30 days after operation 20 men (5%) were readmitted. During a median follow-up of 13 months (IQR 4-28), relapse was observed in 25 men (6%). Unusual sites of recurrence included the peritoneum around the sigmoid and port site in 1 patient each. At the latest follow-up 401 (98%) men were disease free, 3 alive under treatment and 2 had died from progression. Conclusions: In an international cohort, low blood loss and short hospital stay was reported for selected men with small volume retroperitoneal disease undergoing pre- and post-chemotherapy miRPLND. Although complications were rare, miRPLND should only be performed in experienced high-volume centres and surgical teams should be prepared for emergency conversion to open surgery because massive bleeding can occur. Based on encouraging intraoperative safety data together with no concerning signal of peritoneal seeding during the short follow-up period, prospective studies of miRPLND in high volume centres are justified to further evaluate miRPLND technique, complications, functional and oncological outcomes.
    • Localised activation of the EMT switch by peri-neural invading epithelial cells in prostate cancer

      Brown, M.; Hart, C.; Sachdeva, A.; Oliveira, Pedro; Fankhauser, Christian D; Wedge, D; Clarke, Noel W; University of Manchester, Dept. of Genito Urinary Cancer Research, Manchester (2021)
      Introduction & Objectives: Invasion of the peri-neural space by malignant epithelial cell, known as Peri-neural Invasion (PNI), is an acknowledged prostate cancer (PCa) pathological feature associated with recurrence, increased risk of bone metastasis and poor survival. However the molecular mechanism underlying this pathology is relatively unknown. Here we assess the presentation of a metastatic phenotype by the peri-neural invading prostate epithelial cells, their spatial relationship to the tumour lesion and clinical outcome. Materials & Methods: FFPE blocks from an archival cohort (n=54) of radical prostatectomy patients, with associated full clinical history was retrieved under research ethics REC07/H1003/161+5 10_NOCL_02. Serial 4µm sections were stained using an automated multiplex TSA protocol on a Ventana Discovery platform for a panel of metastatic biomarkers (EphA2, pEphA2s897 , pMLC2, E-Cadherin, Vimentin, TOMM20, MTC01, NDUFB8, PTEN) along with the housekeeping landmark markers S100 (neural), pan-cytokeratin and DAPI. Slides were scanned on a Versa 3 platform with Halo image analysis. Prostate spatial zones were defined at 500µm intervals either side of the prostate capsule and pathological features were characterised. Univariate and multivariate (hierarchical clustering, UMap clustering) expression analysis and correlation with clinicopathological features was conducted within GraphPad Prism and R. Results: Marker expression analysis of the pooled (patient independent) PNI showed that all markers have significantly different expression levels dependent on their spatial location in relation to the prostate organ and tumour lesion (Kruskal Wallis p-value <2.2x10-16 except MCT01 (p=5.3x10-10)). Marker expression of amoeboid signalling (EphA2, pEphA2s897 , pMLC2) and mitochondrial defects (loss of Complex I/IV and gain of mitochondrial mass (TOMM20)), associated with a migrational switch to an activated metastatic phenotype in peri-neural invading epithelial cells in PNI close to the prostate edge but outside the tumour lesion correlates with a reduction in overall survival of 28 months (119 months 95%CI 0.3572-1.835 vs 147 months 95% CI 0.5451-2.8; p=0.0249). Conclusions: Peri-neural invading epithelial cells close to the edge of the prostate have features consistent with a switch metastatic behaviour in contrast to the tumour embedded peri-neural invading epithelial cells. This switch was associated with a significant reduction in overall survival.
    • Long term outcomes of Dynamic Sentinel Lymph Node Biopsy (DSNB) for clinically impalpable (cN0) penile cancer patients- an eUROGEN study

      Pozzi, E.; Cakir, O. O.; Castiglione, F.; Schifano, N.; Hadway, P.; Nigam, R.; Rees, R.; Albersen, M.; Parnham, Arie S; Lau, Maurice W; et al. (2021)
      Introduction & Objectives: Dynamic Sentinel Lymph Node Biopsy (DSNB) is routinely offered to patients presenting with penile cancer ³T1G2 and clinically impalpable inguinal lymph nodes (cN0). We aimed to assess the diagnostic accuracy of DSNB, Cancer Specific Survival (CSS) in patients with positive DSNB and positive LN at further Radical Lymph Node groin Dissection (RLND). Materials & Methods: An eUROGEN retrospective study of 509 penile cancer patients undergoing DSNB. Age, type of primary surgery, complications after DSNB, tumour stage, tumour grade were all reported. Number of true positives, true negatives, false negatives and false positives were recorded. False negative was defined as inguinal lymph node recurrence within 12 months from a previous negative DSNB. Sensitivity and specificity of DSNB were calculated. Kaplan-Meier analysis was used to estimate the 5-years CSS and recurrence free-survival rates among patients with positive DNSB and RLND. Results: Overall, 509 patients with cN0 penile cancer were identified. The median follow-up for local recurrence and CSS were 62.5 months (IQR 28.5-91) and 63.5 months (IQR 26.5-90) respectively. All patients underwent DSNB at the time of primary surgery or as a delayed procedure. A total of 993 groins were studied. 37 patients had positive histology at DSNB. 37 patients underwent further RLND with 34 of them having positive histology at RLND. At DSNB true positives were 37 (7.27%), false negatives 3 (0.59). Sensitivity and specificity were 92.5% and 100% respectively. Multivariable Cox regression analysis identified positive LN histology both at DSNB and at RLND as predictors for reduced CSS (HR 4.59, CI: 2.35-8.95, p<0.0001) and (HR 5.64, p=0.0004). Likewise, positive LN histology at DSNB and RLND was a predictor for reduced recurrence free survival HR 4.04 and HR 6.98 all p<0.0001. At Kaplan-Meier analysis, the 5-years CSS for positive LN histology at DSNB/RLND were 69.7% and 69.6% respectively.
    • Outcomes in men undergoing complex circumcision: An aid to consent and litigation

      Issa, Allaudin; Syed, K. B.; Fankhauser, Christian D; Oliveira, Pedro; Parnham, Arie S; Lau, Maurice W; Sangar, Vijay K; The Christie NHS Foundation Trust, Dept. of Urology, Manchester (2021)
      Introduction & Objectives: Circumcision is a common procedure and in complex pathology can be difficult even in expert hands. Litigation for unexpected or poor outcomes is also not uncommon. There is limited data on clinical outcomes in complex circumcision. Here we report initial data from a tertiary referral centre, to highlight complications which may help in consenting of patients. Materials & Methods: A retrospective cohort review of men undergoing a circumcision between 2015 and 2020 was performed. Review of operation notes, pre- & postoperative clinical notes and histology were utilized to record relevant parameters. We included men undergoing complex circumcision which included Redo-circumcision, circumcision for glans adherence (>50%), circumcision with the addition of: wide local excision glans lesion, excision of primary cancer of foreskin, urethral meatal dilatation. Those undergoing circumcision in the setting of a Glansectomy were excluded. Results: Records identified 197 cases of circumcision. Mean age 63.1 yrs, (21 – 92yrs). Of 97 complex circumcisions 24 were performed for pre-operative diagnosis of severe phimosis, 48 for suspected cancer, 13 for lichen sclerosis, 3 were redo circumcisions for residual penile cancer, 7 for PeIN and 2 for severe condylomata. 39 were confirmed cancer cases of which 19 were T1a and 17 T1b. 3 cases revealed T2. Grading of the malignant cases was 7 of grade 1, 15 of grade 2 and 17 grade 3. Complications occurred in 7%: 2 (2%) infections requiring antibiotics, 1 (1%) change in sensation and 1 (1%) patient unhappy with cosmesis. 3 (3%) patients complained of skin tightness. Bleeding, return to theatre within 30 days, erectile dysfunction, wound breakdown and glans dryness occurred at a rate of 0%. Circumcision alongside a further procedure in the same sitting was performed in 29 of the cases including 11 biopsies and 17 wide local excisions of lesions on the glans and 1 urethral dilatation. Positive margins reported in 3 cases they did not experience any post-operative complications. Conclusions: Complex Circumcision can be a difficult procedure. Our data show that when performed at a tertiary centre complications are lower than expected and cosmetic complaints are minimal. When complete this data will be beneficial in consenting and litigation
    • Post traumatic growth during COVID-19: unity in diversity

      Lakha, M. A.; Bhowmik, A.; Bisht, S.; Shrestha, S.; Gajanan, Kantappa; Shah, S.; Wrightington Wigan & Leigh NHS Foundation Trust (2021)
      Aims This poster reflects how the experience of staying with people of diverse nations and cultural background helped the stranded IMGs cope with this agony in a foreign land during an unprecedented tumultuous situation. The aim is to show that despite diversity among people, the hard times made them unite and overcome countless difficulties. Background The COVID 19 pandemic has been a period of global health crisis and has exponentially affected mental health issues in the world population. In these difficult times, several International Medical Graduates (IMGs), who had come to the UK to attend their PLAB exams, were left stranded as the exams were postponed, flights cancelled and borders sealed. Faced with huge uncertainty their mental health was of great concern. At this time the British Association of Physicians of Indian Origin (BAPIO) came forward to help this cohort of stranded doctors in terms of accommodation, finances, mental health support, preparation for exams to the extent of liaising with General Medical Council (GMC) and Home Office. The virtual support group provided a platform for IMGs from different nations and cultures to get in touch with each other helping overcome mental burden and stress. The stories presented in the poster show how unity in diversity helped these young doctors deal with mental trauma amidst the Pandemic. Method 276 doctors from 27 countries were looked after by BAPIO. From those excerpts taken from 26 IMGs, personal narratives was used as a method for qualitative assessment. The percentage of IMGs clearing their exams and getting jobs in the NHS has been used for quantitative assessment. Result Qualitative: The personal narratives of the IMGs show how they were positively impacted by staying together albeit different nationalities and cultural background. Quantitative: A total of 21 IMGs out of the 26 cleared their PLAB 2 exams and got registration under General Medical Council giving a percentage of 81.7%. 20 IMGs have successfully joined the NHS in various posts giving a job success rate of 95.2%. Conclusion The experience of living and sharing housings with people from different nationalities, has increased appreciation and also prepared them to work in the NHS which has a diverse work force. This learning experience has been integral for all of us in shaping our life in the UK making everyone more compassionate.
    • Druggable molecular alterations in bile duct cancer: potential and current therapeutic applications in clinical trials

      Bourien, H.; Lamarca, Angela; McNamara, Mairead G; Hubner, Richard A; Valle, Juan W; Edeline, J; Department Of Medical Oncology, Centre Eugène Marquis, Rennes, France, France (2021)
      Introduction: Cholangiocarcinomas (CCA) are rare tumors that are associated with a variety of molecular alterations. Many of these alterations are now actionable using drugs currently in development, and CCA may be a perfect example of application of a precision oncology approach. However, development of drugs in CCA faces the challenge of targeting rare alterations in a rare disease.Areas covered: In this review, we present the current data on targeted therapies in development for CCA, focusing on IDH1, FGFR2, BRAF, and HER2 alterations. We also discuss rationale for targeting other alterations, currently without specific development in CCA. We searched PubMed and google scholar in February 2021 for relevant articles and presentation in recent congress regarding the literature on molecular alterations, drugs in cholangiocarcinomas and biliary tract cancers.Expert opinion: Despite a strong rationale and promising early results, applying a precision oncology approach in CCA for everyday patients is still exposed to significant challenges: obtaining the molecular portrait of these tumors due to difficulties with biopsy access, complexities of drug development in subgroups of these relatively rare tumors, and sub-optimal access to drugs outside clinical trials.
    • Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group

      Koessler, T.; Alsina, M.; Arnold, D.; Ben-Aharon, I.; Lutz, M. P.; Obermannova, R.; Peeters, M.; Sclafani, F.; Smyth, E.; Valle, Juan W; et al. (2021)
      Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice
    • A narrative review of primary research endpoints of neoadjuvant therapy for lung cancer: past, present and future

      Ren, S.; Xu, A.; Lin, Y.; Camidge, D. R.; Di Maio, M.; Califano, Raffaele; Hida, T.; Rossi, A.; Guibert, N.; Zhu, C; et al. (2021)
      Objective: This review summarizes the current status of neoadjuvant therapy and discusses the choice of new clinical research endpoints for non-small cell lung cancer. Background: Neoadjuvant chemotherapy is a recognized practice in patients with resectable and locally advanced lung cancer. With the introduction of molecular targeted drugs and immune checkpoint inhibitors (ICIs), the overall survival (OS) of patients with lung cancer has been significantly improved, and the original traditional clinical research endpoints are no longer suitable for existing clinical research. In order to accelerate the process of clinical trials and the development and approval of drugs, it is necessary to find suitable alternative indicators as the main indicators of clinical research. Methods: Therefore, this article focuses on clinical trials using disease-free survival (DFS), progression free survival, and pathological evaluation indicators, pathologic complete response and major pathologic response, as surrogate endpoints. We search related literature through PubMed database and clinical trials through clinicaltrials.gov. Conclusions: Pathologic complete response and major pathologic response are recommended as surrogate endpoints in the era of neoadjuvant immunotherapy, and secondary endpoints are listed for the prediction of pathological results. In addition, the definitions of major pathological response (MPR) and PCR should be standardized, and a new pathological evaluation standard should be developed, which is applicable to all current treatment methods.
    • Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC

      Doebele, R. C.; Perez, L.; Trinh, H.; Martinec, M.; Martina, R.; Riehl, T.; Krebs, Matthew G; Meropol, N. J.; Wong, W B; Crane, G.; et al. (2021)
      Aim: Generating direct comparative evidence in prospective randomized trials is difficult for rare diseases. Real-world cohorts may supplement control populations. Methods: Entrectinib-treated adults with advanced ROS1 fusion-positive NSCLC (n = 94) from Phase I/II trials (ALKA-372-001 [EudraCT2012-00148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]) were compared with a real-world crizotinib-treated cohort (n = 65). Primary end point, time-to-treatment discontinuation (TTD); secondary end points, PFS and OS. Results: Median (95% CI) weighted TTD: 12.9 (9.9-17.4) months for entrectinib; 8.8 (6.2-9.9) months for crizotinib (weighted hazard ratio, 0.72 [0.51-1.02]). Median OS with entrectinib was not reached, weighted median OS with crizotinib was 18.5 (15.1-19.9) months. Conclusion: Entrectinib administered in clinical trials may be associated with longer TTD than a real-world crizotinib population.
    • The internal dosimetry user group position statement on molecular radiotherapy

      Gear, J.; McGowan, D.; Rojas, B.; Craig, A. J.; Smith, A. L.; Scott, C. J.; Scuffam, J.; Aldridge, M; Tipping, Jill; The Internal Dosimetry User Group, England, United Kingdom (2021)
      The Internal Dosimetry User Group (IDUG) is an independent, non-profit group of medical professionals dedicated to the promotion of dosimetry in molecular radiotherapy (www.IDUG.org.uk). The Ionising Radiation (Medical Exposure) Regulations 2017, IR(ME)R, stipulate a requirement for optimisation and verification of molecular radiotherapy treatments, ensuring doses to non-target organs are as low as reasonably practicable. For many molecular radiotherapy treatments currently undertaken within the UK, this requirement is not being fully met. The growth of this field is such that we risk digressing further from IR(ME)R compliance potentially delivering suboptimal therapies that are not in the best interest of our patients. For this purpose, IDUG proposes ten points of action to aid in the successful implementation of this legislation. We urge stakeholders to support these proposals and ensure national provision is sufficient to meet the criteria necessary for compliance, and for the future advancement of molecular radiotherapy within the UK.
    • Risk of infectious complications in adult patients after allogeneic hematopoietic stem cell transplantation depending on the site of central venous catheter insertion-multicenter prospective observational study, from the IDWP EBMT and Nurses Group of EBMT

      Snarski, E.; Stringer, Jacqui; Mikulska, M.; Gil, L.; Tridello, G.; Bosman, P.; Lippinkhof, A.; Hoek, J.; Karas, M.; Zver, S.; et al. (2021)
      The current guidelines for prevention of infections in hematopoietic stem cell transplantation (HSCT) do not specify which central venous catheter (CVC) insertion site should be preferred in allogeneic HSCT recipients-internal jugular vein (IJV) or subclavian vein (SCV). We designed a multicenter prospective observational study comparing the risk of infectious and non-infectious complications between the two most common sites of CVC insertion (IJV and SCV) in allogeneic HSCT. There were in total 232 consecutive patients (86 IJV and 146 SCV) who underwent adult allogeneic HSCT reported from 11 centers in 8 countries. The center independent analysis of central line associated/related blood stream infections with ECDC criteria has shown statistically significant difference favoring SCV (23% IJV vs 13% SCV (OR 2.03 (1.01-4.06), p = 0.047)). The differences in CLABSI per 1000 days of CVC use favored SCV over IJV (7.93/1000 days IJV vs 2.79/1000 days SCV, p = 0.002). The frequency of all non-infectious complications was similar in both arms-13% IJV and 12% SCV (OR 1.1 (0.5-2.5), p = 0.8). This multicenter prospective study showed statistically significant lower confirmed number of CLABSI per 1000 days of CVC use without higher risk of noninfectious complications related to the subclavian insertion site in allogeneic HSCT recipients.
    • A phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial

      Banerjee, S. N.; Tang, M.; O'Connell, R. L.; Sjoquist, K.; Clamp, Andrew R; Millan, D.; Nottley, S.; Lord, R.; Mullassery, V. M.; Hall, M.; et al. (2021)
      Background: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. Methods: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. Results: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. Conclusions: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.
    • On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

      Lindsay, Colin R; Garassino, M. C.; Nadal, E.; Öhrling, K.; Scheffler, M; Mazières, J.; Division of Cancer Sciences, University of Manchester, Manchester, UK (2021)
      Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRASG12C, the most common mutation, is found in ~13% of patients. While KRAS was long considered 'undruggable', several novel direct KRASG12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy.
    • Perineal urethrectomy in the anterior compartment for pelvic exenteration

      Solomon, M.; Sutton, Paul A; Lee, P; Austin, K.; Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (2021)
      None
    • Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

      Morra, A.; Escala-Garcia, M.; Beesley, J.; Keeman, R.; Canisius, S.; Ahearn, T. U.; Andrulis, I. L.; Anton-Culver, H.; Arndt, V.; Auer, P. L.; et al. (2021)
      Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
    • Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients: polyfunctional immune responses and lessons for clinical practice

      Stadtmauer, E. A.; Sullivan, K. M.; El Idrissi, M.; Salaun, B.; Alonso Alonso, A.; Andreadis, C.; Anttila, V. J.; Bloor, Adrian; Broady, R.; Cellini, C.; et al. (2021)
      Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.
    • Long-term efficacy update of crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumour from EORTC trial 90101 CREATE

      Schöffski, P.; Kubickova, M.; Wozniak, A.; Blay, J. Y.; Strauss, S. J.; Stacchiotti, S.; Switaj, T.; Bücklein, V.; Leahy, Michael G; Italiano, A.; et al. (2021)
      Purpose: European Organisation for Research and Treatment of Cancer (EORTC) 90101 (CREATE) was a prospective, multicentric, non-randomised, open-label phase II basket trial to assess the efficacy and safety of crizotinib in patients with different types of cancers, including advanced inflammatory myofibroblastic tumour (IMT) with or without anaplastic lymphoma kinase (ALK) rearrangements. Here, we report updated results with long-term follow-up. Patients/methods: After central reference pathology, eligible ALK-positive and ALK-negative patients with advanced/metastatic IMT deemed incurable with surgery, radiotherapy or systemic therapy received oral crizotinib 250 mg twice daily. The ALK status was assessed centrally using immunohistochemistry and fluorescence in situ hybridisation. The primary end-point was the proportion of patients who achieved an objective response (i.e. complete or partial response). If ≥6 ALK-positive patients achieved a confirmed response, the trial would be deemed successful. Results: At data cut-off on 28th January 2021, we performed the final analysis of this trial. Of the 20 eligible and treated patients (19 of whom were evaluable for efficacy), with a median follow-up of 50 months, five were still on crizotinib treatment (4/12 ALK-positive and 1/8 ALK-negative patients). The updated objective response rate (ORR) was 66.7% (95% confidence interval [CI] 34.9-90.1%) in ALK-positive patients and 14.3% (95% CI 0.0-57.9%) in ALK-negative patients. In the ALK-positive and ALK-negative patients, the median progression-free survival was 18.0 months (95% CI 4.0-NE) and 14.3 months (95% CI 1.2-31.1), respectively; 3-year overall survival rates were 83.3% (95% CI 48.2-95.6) and 34.3% (95% CI 4.8-68.5). Safety results were consistent with previously reported data. Conclusion: These updated results confirm previous findings that crizotinib is effective, with durable responses, in patients with locally advanced or metastatic ALK-positive IMT. With further follow-up after the original primary analysis, the ORR increased, as patients derived long-term benefit and some responses converted from stable disease to partial responses.