A 60-year-old male presented in 2021 with pulmonary metastatic epitheloid mesothelioma. Notable history included psoriasis and T4aN2bM0 sarcomatoid squamous-cell-carcinoma of the oral-cavity treated with palliative radiotherapy. Due to an extraordinary response to radiotherapy, Head and Neck Multidisciplinary-Team-Meeting re-review felt a lymphomatoid process more likely. For mesothelioma, he completed 4 cycles of palliative pemetrexed/ carboplatin chemotherapy with partial-response but then stopped due to bone-marrow toxicity. Over 18 months, surveillance imaging revealed slow nodal disease-progression.

INTRODUCTION:As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication are paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (albumin <35 g/L, lactate dehydrogenase >450 IU/L, sodium <135 mmol/L), is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era. METHODS:We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and C-index was used to compare predictive ability of prognostic models. RESULTS:Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS, and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95% CI: 1.01-6.24, p = 0.049; HS 2/3 vs. 0: 10.32, 95% CI: 2.15-49.62, p = 0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95% CI: 1.12-26.57, p = 0.036; RMS 3 vs. 0/1 6.83, 95% CI: 1.15-40.53, p < 0.001; C-index 0.743). CONCLUSIONS:HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT.

Brain metastases are the most common intracranial tumour and affect approximately 20% of adult cancer patients, most commonly from lung, breast, melanoma, and kidney cancer. However, the true incidence of brain metastasis is unknown. England’s cancer registration system only reliably captures brain metastases present at diagnosis (rather than those that develop later), and the same is true for US-based data. Although it is relatively easy to identify patients receiving some treatments for brain metastases (surgery, stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT)), identifying those receiving chemotherapy or no treatment is much harder. As a result, the existing literature is heavily biased towards reporting treated populations. This study attempts to find an unbiased estimate of the true number of patients developing brain metastases, based on data from a single centre. Cases of brain metastasis were retrospectively identified from the radiology information system database (SolitonTM). We performed a Boolean search for specific keywords in the radiology reports of all CT and MRI head scans performed at the trust between 1st January 2018 and 31st December 2019. The following keywords were searched for “metastases”, “metastatic“, “metastasis”, “mets”, “deposit”, “deposits”, “secondaries”, “secondary” and “disseminated”. Duplicate cases were then removed and the subsequent list was manually reviewed We identified all patients who received any treatment for brain metastases who were diagnosed at our centre. We only included patients with newly diagnosed brain metastases (included: leptomeningeal; excluded: skull-based metastases). We excluded patients who were diagnosed in other centres and treated here or diagnosed outside the study period. We then extracted data on primary diagnosis, admissions, and survival. 1192 patients had a CT or MRI of the head with a mention of “brain metastases” in the report; of these 305 were newly diagnosed with brain metastases during the study period (432 had metastases; 127 diagnosed earlier). Of these 305 patients, 217 (71.1%) were treated locally (SRS = 88; WBRT = 74; surgery = 88; systemic therapy = 16; multiple treatments = 45) and 10 (3.3%) were referred elsewhere. 78 (25.6%) patients received no treatment. Of the 217 treated patients, 124 were female, and the median age was 61. Of the 78 untreated patients, 38 were females, and the median age was 70 years old. The commonest primary diagnoses in both groups were lung (39%) and breast (21%) cancer. 16 (21%) of the untreated patients had an unbiopsied primary tumour. Median survival for patients having (any) treatment was 52 weeks compared to 5 weeks for those not having treatment. We have presented an unbiased single-centre estimate of brain metastases occurrence. Unlike previous work, we manually reviewed all imaging reports that suggested metastasis, and included all patients diagnosed with brain metastases at any timepoint. We reduced the bias associated with being a tertiary centre by only including patients who were diagnosed here, rather than referred from other centres. 25% of our cohort received no treatment, and survival in this group is poor. This is broadly in line with the only other study on this topic (Bentley, 2019) that reported a large minority (39%) of untreated patients. Our key conclusions are: When assessing the incidence of brain metastases, studies that do not account for untreated patients are likely to significantly underestimate incidence, and over-estimate survival. Improving outcomes in patients with brain metastases might be best achieved by addressing earlier identification and intervention in those who currently receive no treatment