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.

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.

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.

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.

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

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 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.

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.

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.

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.