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Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival.SCORAD is a randomised trial of 686 patients comparing a single dose of 8 Gy radiotherapy with 20 Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). A multivariable Cox regression for overall survival (OS) and a logistic regression for ambulatory status at 8 weeks were performed in the training set using baseline factors and a backward selection regression to identify a parsimonious model with p ≤ 0.10. Receiver Operating Characteristic (ROC) analysis evaluated model prognostic performance in the validation set. Validation of the final survival model was performed in a separate registry dataset (n = 348).The survival Cox model identified male gender, lung, gastrointestinal, and other types of cancer, compression at C1-T12, presence of non-skeletal metastases and poor ambulatory status all significantly associated with worse OS (all p 0.05). The ROC AUC for the selected model was 75% (95%CI: 69-81) in the SCORAD validation set and 68% (95%CI: 62-74) in the external validation registry data. The logistic model for ambulatory outcome identified primary tumour breast or prostate, ambulatory status grade 1 or 2, bladder function normal and prior chemotherapy all significantly associated with increased odds of ambulation at 8 weeks (all p 0.05). The ROC AUC for the selected model was 72.3% (95% CI 62.6-82.0) in the validation set.Primary breast or prostate cancer, and good ambulatory status at presentation, are favourable prognostic factors for both survival and ambulation after treatment.

Acute kidney injury (AKI) is a common complication among oncology patients associated with lower remission rates and higher mortality. To reduce the impact of this condition, we aimed to predict AKI earlier than existing tools, to allow clinical intervention before occurrence. We trained a random forest model on 597,403 routinely collected blood test results from 48,865 patients undergoing cancer treatment at The Christie NHS Foundation Trust between January 2017 and May 2020, to identify AKI events upcoming in the next 30 days. AKI risk levels were assigned to upcoming AKI events and tested through a prospective analysis between June and August 2020. The trained model gave an AUROC of 0.881 (95% CI 0.878–0.883), when assessing predictions per blood test for AKI occurrences within 30 days. Assigning risk levels and testing the model through prospective validation from the 1st June to the 31st August identified 73.8% of patients with an AKI event before at least one AKI occurrence, 61.2% of AKI occurrences. Our results suggest that around 60% of AKI occurrences experienced by patients undergoing cancer treatment could be identified using routinely collected blood results, allowing clinical remedial action to be taken and disruption to treatment by AKI to be minimised.

We evaluated the outcomes for patients with peripheral T-cell lymphoma (PTCL) undergoing front-line chemotherapy at our institutions between 2002 and 2012. One hundred and fifty-six patients were eligible, comprising PTCL not otherwise specified (NOS) (n = 50, 32.0%), angioimmunoblastic T-cell lymphoma (AITL) (n = 44, 28.2%), anaplastic large-cell lymphoma (ALCL) ALK negative (n = 23, 14.7%), ALCL ALK positive (n = 16, 10.3%), and other (n = 23, 14.7%). Most patients received CHOP (66.0%) and 13.0% received an autologous hematopoietic progenitor cell transplant (HPCT). With a median follow-up of 63.4 months, 5-year overall survival (OS) and progression-free survival (PFS) was 38.8% and 19.8% respectively. Independent risk factors for inferior OS were age60 years, International Prognostic Index (IPI) ≥ 2 and lack of complete response to induction. When responding patients were compared by receipt of an autologous HPCT versus not, HPCT was associated with improved PFS (p = .001) and OS (p = .046) and remained significant for PFS in multivariate analysis suggesting a possible therapeutic benefit.

Primary brain cancer and other tumors of the central nervous system are relatively rare but are important because of their poor prognosis. For example, in the United Kingdom (UK), the overall annual incidence is about 7 per 100 000 people. They account for 2% of all cancers diagnosed, but the 5-year survival rates are the fourth lowest of the 21 most common cancers in England.1 Moreover, brain tumors affect a disproportionately high number of people of working age (less than aged 65 years)2 and are the third most common cause of cancer death in the age group 15–34 years. The majority (86%) of brain tumors are gliomas,3,4 and these have a poor prognosis with median survival of around 12 months and

Since the identification of the BRCA1 and BRCA2 genes speculation has continued regarding the breast and ovarian cancer risk associated with mutations in these genes. Also, as to whether mutations in these genes account for the majority of the association between breast and ovarian cancer. Identification of RAD51C and RAD51D mutations in breast/ovarian cancer families has reawakened the debate as to whether it is safe to reassure women from BRCA negative families that they are not at increased risk of ovarian cancer. 1433 women from breast cancer families that had tested negative for BRCA1/2 were followed for a total of between 0.04 and 25 years and checked against a cancer registry for ovarian cancer incidence. Data was censored at ovarian cancer diagnosis, oophorectomy or death. During 16358 women years of follow up no invasive epithelial ovarian cancer occurred, although 2 borderline tumors were diagnosed. Expected rates for this cohort from cancer registry data were 2.75 epithelial ovarian tumors with 2.52 for invasive cancer and 0.23 for borderline tumors. The upper confidence limit for invasive RR was 1.3 and for borderline tumors 0.97–31. In conclusion this the largest prospective follow up of a BRCA negative cohort has demonstrated that there is no increase in risk of invasive ovarian cancer in families that have tested negative for BRCA1/2. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-01.

BACKGROUND: There has been a steady increase in published research from Europe and North America on the epidemiology of cancers in young people. There are limited data from the developing world. We contrast the incidence of cancer at ages 15-29 years in India and England. PROCEDURE: Malignant neoplasms in those aged 15-29 years registered during 2001-2003 in five urban population-based cancer registries (PBCRs) of India and in eight PBCRs in England were included. Site-based classification was used. Age-standardized incidence rates were expressed per 100,000 person years. RESULTS: In India, 4,864 (5.8%) of 84,450 cases and in England, 8,137 (1.2%) of 65,6752 cancer cases occurred in those aged 15-29 years. For this age group, the incidence rate for males and females in India were 12.91 and 14.19, and in England were 27.75 and 28.88, respectively. In males aged 15-29 years, the three most common cancers in India were leukemia, lymphoma, and central nervous system tumors and in England were cancers of male genital organs, lymphoma, and leukemia. Cancers of female genital organs, breast, and leukemia were most common in females in India and cancers of female genital organs, lymphoma, and melanoma in England. For cancers of mouth, stomach, and gall bladder, the incidence was higher in India. CONCLUSION: Incidence of cancer at ages 15-29 years in England is higher at most sites than in India. Variation in environmental exposures between the two countries might be an explanation. Under-ascertainment of cases and gender bias in seeking healthcare may also influence reported incidence rates in India.

Introduction Dose escalation has been shown to improve biochemical outcome in localised prostate cancer. An HDR brachytherapy boost is an effective strategy for dose escalation, since it exploits the low α/β ratio in prostate cancer, allowing the delivery of a high biological dose to the tumour. We sought to evaluate the biochemical disease free survival in patients with intermediate and high risk localised prostate cancer treated with EBRT plus HDR brachytherapy as a boost, in our institution. Patients and methods Biochemical outcome was collected prospectively in 95 patients treated from 2008 to 2010, with an HDR boost of 12.5Gy followed by EBRT delivered as 37.5Gy in 15 fractions over 3weeks. The ASTRO definition of biochemical failure (2μg/L above PSA nadir) was used as the outcome measure. 61/95 (64%) were classified as high risk (stage>T2b or PSA>20μg/L or Gleason score>7) while 34/95 (36%) were intermediate risk. 92/95 (97%) patients received neoadjuvant androgen deprivation therapy (ADT). Adjuvant hormone therapy was at the discretion of the treating clinician. Results The median follow-up for the cohort was 65months (range, 18–88) with a 5-year biochemical DFS of 80.5% (95% Confidence Interval [CI]: 72.8–89.0). The prognostic factors used in the analysis model were: clinical stage, presenting PSA, duration of ADT, Gleason score, risk category, prostate volume, D90 and V100. Only presenting PSA (HR 1.03; CI 1.00–1.05, p =0.03) predicted for a poorer biochemical DFS on multivariate analysis. Conclusion These data confirm that EBRT plus a single-fraction HDR brachytherapy boost achieves good biochemical control in a cohort of predominantly high risk patients.

Aims We aimed to describe and compare survival in teenagers and young adults (TYAs) with cancer to that of younger children and older adults, to identify sub-populations at greater or lesser risk of death. Methods We compared survival in cancer patients diagnosed in the United Kingdom aged 13–24 years (TYAs) to those aged 0–12 (children) and 25–49 years (adults) using the National Cancer Data Repository. All cases had a first cancer diagnosis between 1st January 2001 and 31st December 2005 with censor date 31st December 2010 or death if earlier. Results We found six distinct statistically significant survival patterns. In pattern 1, the younger the age-group the better the 1- and 5-year survival (acute lymphoid leukaemia, carcinoma of ovary and melanoma). In pattern 2, TYAs had a worse 5-year survival than both children and young adults (bone and soft tissues sarcomas). In pattern 3, TYAs had a worse 1-year survival but no difference at 5-years (carcinoma of cervix and female breast). In pattern 4, TYAs had better 1-year survival than adults, but no difference at 5 years (carcinoma of liver and intrahepatic bile ducts, germ cell tumours of extra-gonadal sites). In pattern 5, the younger the age-group the better the 5-year survival, but the difference developed after 1-year (acute myeloid leukaemia, carcinoma of colon and rectum). In pattern 6, there was no difference in 1- and 5-year survival between TYAs and adults (testicular germ cell tumours, ovarian germ cell tumours and carcinoma of thyroid). Conclusion TYAs with specific cancer diagnoses can be grouped according to 1- and 5-year survival patterns compared to children and young adults. To further improve survival for TYAs, age-specific biology, pharmacology, proteomics, genomics, clinician and patient behaviour studies embedded within clinical trials are required.

Background The national confidential enquiry into patient outcomes and death (NCEPOD) set important benchmarks in assessing the quality of care received by patients dying within 30 days of systemic anticancer therapy (SACT). Monthly morbidity and mortality audits conducted to recommendations in the NCEPOD were commenced at the Christie NHS Foundation Trust in 2009, specifically to assess and improve patient outcomes. Methods We evaluated the outcomes of patients who died within 30 days of SACT over a 4 year period 2009–2013. We collated audit findings to determine the number of treatment related deaths, clinical characteristics of patients, causes of death and quality of care received. We examined the benefit of the audit in decreasing 30 day mortality during the 4 years and considered factors that may be associated with an increased risk of SACT related death. Results A total of 31,183 patients were treated at the Christie from 2009 to 2013. Of these 4% died within 30 days of SACT. Death was treatment related in 11%. The decision to treat with SACT was appropriate in 87% of but there was room for improvement in care in 24%. Mortality decreased over the 4 years. Possible factors associated with 30 day mortality post SACT included performance status ⩾2, presence of comorbidities, treatment type and treatment setting. Conclusions We demonstrated that our audit process is feasible and robust. Further areas of research to determine predictive scores for patient treatment selection and improve outcomes were highlighted and are ongoing.

Background Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families. Patients and Methods A prospective study involving women seen at a single family history clinic in Manchester, UK. Patients were excluded if they had ovarian cancer or oophorectomy prior to clinic. Follow-up was censored at the latest date of: 31/12/2010; ovarian cancer diagnosis; oophorectomy; or death. We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population. Results We studied 8005 women from 895 families. Women from BRCA2 mutation families showed a 17-fold increased risk of invasive ovarian cancer (relative risk (RR) 16.67; 95% CI 5.41 to 38.89). This risk increased to 50-fold in women from families with BRCA1 mutations (RR 50.00; 95% CI 26.62 to 85.50). No association was found for women in families tested negative for BRCA1/2, where there was 1 observed invasive ovarian cancer in 1613 women when 2.74 were expected (RR 0.37; 95% CI 0.01 to 2.03). There was no association with ovarian cancer in families untested for BRCA1/2 (RR 0.99; 95% CI 0.45 to 1.88). Discussion This study showed no increased risk of ovarian cancer in families that tested negative for BRCA1/2 or were untested. These data help counselling women from BRCA1/2 negative families with breast cancer that their risk of invasive ovarian cancer is not higher than the general population.

Urological tumours are the third most frequent malignancy in Lynch syndrome after colonic and endometrial cancer. Upper urinary tract tumours are well recognised in Lynch syndrome, but the association with prostate and bladder cancer is controversial. We determined the incidence and cumulative and relative risks of prostate and bladder cancer in a cohort of Lynch syndrome families. Male Lynch syndrome mutation carriers and their genetically untested male first degree relatives (FDR) were identified from the Manchester Regional Lynch syndrome database (n = 821). Time to the development of urological cancer was identified for each urological site (renal pelvis, ureter, bladder and prostate). Cumulative and relative risks were calculated, with results classified by mutation carrier status and specific causative genetic mutations. Eight prostate cancers were identified, only one occurring before the age of 60. Analysis of person-years at risk of prostate cancer by Lynch syndrome mutation carrier status suggests a correlation between MSH2 mutation carriers and a tenfold increased risk of prostate cancer (RR 10.41; 95 % CI 2.80, 26.65). No such association was found with bladder cancer (RR 1.88; 95 % CI 0.21, 6.79). The association of upper urinary tract tumours with MSH2 and MLH1 mutations was confirmed. We have carried out the largest study of male Lynch syndrome mutation carriers to establish the risks of urological malignancy. A tenfold increased risk of prostate cancer is supported in MSH2 with mutation carriers having roughly double the risk of prostate cancer to FDRs. A trial of PSA testing in MSH2 carriers from 40 to 50 years may be justifiable.

The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of “other cancers” in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1–6.0) and stomach at 2.4 (95% CI 1.2–4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9–7.8) and prostate (RR 6.3, 95% CI 4.3–9.0) and uveal melanoma (RR 99.4, 95% CI 11.1–359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9–7.8) and stomach (RR 2.7, 95% CI 1.3–4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.

Neurofibromatosis 1 (NF1) is a comparatively common autosomal dominant disorder. However, relatively few studies have assessed lifetime risk; and information about the effect of NF1 on mortality remains uncertain. NF1 patients were identified using The North West regional family Genetic Register, which covers the 4.1 million people living in North West England, including the regions of Greater Manchester, Cheshire and Cumbria. Data relating to tumours and malignancies were obtained from The North West Cancer Intelligence Service. Death data for the general North West population were obtained from the Office of National Statistics. We identified 1186 individuals with NF1, of whom 1023 lived within the strict regional boundaries (constituting a region of North West England bound by The Pennines to the east and Irish Sea to the west, but excluding the conurbation of Liverpool (Merseyside) and the Wirral peninsula) and 131 had died. MPNST and glioma were found to be the two most common causes of reduced life expectancy among NF1 patients. In Kaplan–Meier analyses the median survival for NF1 patients was shown to be 71.5 years, with women living ∼7.4 years longer than men. On average both men and women lived ∼8 years less than their counterparts in the general population. Reduction in life expectancy for NF1 patients was found to be much lower (8 years) than the previously estimated 15-year decrease. Limitations relating to the underreporting of NF1 on death certificates were once again highlighted and should be considered in future investigations.

There has been a steady increase in published research from Europe and North America on the epidemiology of cancers in young people. There are limited data from the developing world. We contrast the incidence of cancer at ages 15-29 years in India and England.Malignant neoplasms in those aged 15-29 years registered during 2001-2003 in five urban population-based cancer registries (PBCRs) of India and in eight PBCRs in England were included. Site-based classification was used. Age-standardized incidence rates were expressed per 100,000 person years.In India, 4,864 (5.8%) of 84,450 cases and in England, 8,137 (1.2%) of 65,6752 cancer cases occurred in those aged 15-29 years. For this age group, the incidence rate for males and females in India were 12.91 and 14.19, and in England were 27.75 and 28.88, respectively. In males aged 15-29 years, the three most common cancers in India were leukemia, lymphoma, and central nervous system tumors and in England were cancers of male genital organs, lymphoma, and leukemia. Cancers of female genital organs, breast, and leukemia were most common in females in India and cancers of female genital organs, lymphoma, and melanoma in England. For cancers of mouth, stomach, and gall bladder, the incidence was higher in India.Incidence of cancer at ages 15-29 years in England is higher at most sites than in India. Variation in environmental exposures between the two countries might be an explanation. Under-ascertainment of cases and gender bias in seeking healthcare may also influence reported incidence rates in India.

Introduction: PTCL is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) comprising ~10% of cases. CHOP is frequently used first-line, but with the exception of ALK+ anaplastic large-cell lymphoma (ALCL), long term outcomes are historically poor with reported 5-yr overall survival (OS) rates of 36%. We retrospectively evaluated the outcomes following first-line chemotherapy for patients with PTCL treated at the Royal Marsden (RM) and Christie (CH) hospitals over a 10-year period. Methods: All eligible patients with PTCL aged ≥18 years and treated at the RM and CH between 1st January 2002 and 31st January 2012 were included. The study was approved by our institutional review boards. Patients were identified from hospital databases and included if they had received at least 1 cycle of first-line chemotherapy. Precursor T-cell malignancies, mycosis fungoides and adult T-cell leukaemia/lymphoma were excluded, as was cutaneous T-cell lymphoma not requiring combination chemotherapy. Clinical data were collated from electronic patient records and the diagnosis of PTCL was confirmed in all cases by an expert haematopathologist. Response was assessed using the IWG 1999 criteria. OS and progression free survival (PFS) were calculated from date of start of 1st line treatment and analysed using Kaplan Meier methods and Cox regression model. The impact of clinical factors on survival was assessed using Cox regression analysis. Results: A total of 143 (RM n=69, CH n=74)patients were evaluable and the median follow-up was 63.4 months. The median age at diagnosis was 59 yrs (range 18-89 yrs). PTCL subtypes were: PTCL not otherwise specified (NOS) (n=48), angioimmunoblastic T-cell lymphoma (AITL) (n=37), ALCL ALK- (n=24), ALCL ALK+ (n=14) and other (n=20). First-line chemotherapy included CHOP (n=97), GEM-P (gemcitabine, cisplatin and methylprednisolone) (n=16), other gemcitabine containing regimen (n=7), asparaginase (n=2) or other (n=21). OS by PTCL subtype is shown in Figure 1. Response was evaluable for 125/143 patients. Overall response (ORR) to first-line chemotherapy was 81.4% with complete response (CR) seen in 42.4%. For the entire cohort (n=143) 5-yr PFS was 20.6% and 5-yr OS was 39.6%. For CHOP treated patients ORR was 80.5% with CR in 43.7%, 5-yr PFS was 25.5% and 5-yr OS was 41.2%. ORR with GEM-P was 78.6% with CR in 50%, 5-yr PFS was 13.6% and 5-yr OS was 39.1%. No statistically significant difference between CHOP and GEM-P was seen in terms of response, OS or PFS. Autologous stem cell transplantation (autoSCT) was performed post first-line induction in 15% (n=22). For patients in CR post induction (CR1) (n=41), we compared survival for those treated with (n=12) and without (n=29) subsequent autoSCT. AutoSCT in CR1 was associated with a trend towards better PFS (HR 0.36, 95%CI 0.13-1.02; p=0.056) but not OS (HR 0.72, 95% CI 0.21-2.47; p=0.599). Uni- (UVA) and multivariate analyses (MVA) were performed to determine the impact of the following on OS and PFS: age (≤60 vs > 60yrs), gender, stage (I-III vs IV), performance status (PS, 0-1 vs 2), B symptoms (present vs absent), ethnicity (white vs other), LDH (normal vs elevated), IPI (low vs intermediate vs high), PTCL subtype, number of extranodal sites (0-1 vs >1), chemotherapy (CHOP vs gemcitabine based vs other), CR post induction (present vs absent) and autoSCT (performed vs not). Factors with a p-value of Conclusion: With the exception of ALK+ ALCL, outcomes for PTCL following first-line chemotherapy remain disappointing and a more effective induction regimen is urgently required. Our data indicates that achieving a CR with first-line induction is a key factor for optimising OS and PFS. To this end, the currently accruing UK NCRI randomised phase II CHEMO-T study is comparing CHOP with GEM-P as first-line regimens in PTCL. AutoSCT in CR1 may offer a PFS benefit and should be considered in eligible patients. Table 1. MVA for OS and PFS (n=104) Risk Factor HR 95% CI p-value OS Intermediate risk IPI 4.56 1.79-11.6 0.001 High risk IPI 12.0 4.32-33.1 Figure 1. OS according to PTCL subtype Figure 1. OS according to PTCL subtype Disclosures Chau: Roche: Research Funding. Cunningham:Merrimack: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; Medimmune: Research Funding; Astra Zeneca: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Merck Serono: Research Funding; Sanofi: Research Funding.

BACKGROUND: Although relatively rare, cancer in teenagers and young adults (TYA) is the most common disease-related cause of death and makes a major contribution to years of life lost in this age group. There is a growing awareness of the distinctive needs of this age group and drive for greater understanding of how outcomes can be improved. We present here the latest TYA survival trends data for the United Kingdom (UK). METHODS: Using national cancer registry data, we calculated five-year relative survival for all 15-24year olds diagnosed with cancer or a borderline/benign CNS tumour in the UK during the periods 1992-1996, 1997-2001 and 2002-2006. We analysed trends in survival for all cancers combined and for eighteen specified groups that together represent the majority of TYA cancers. We compared our data with published data for Europe, North America and Australia. RESULTS: Five-year survival for all cancers combined increased from 75.5% in 1992-1996 to 82.2% in 2002-2006 (P