The archaeological potential of the northern Luangwa Valley, Zambia: The Luwumbu basin.

The Luangwa Basin, Zambia, which forms part of the Zambezi drainage, is strategically located between the Central African plateau and the East African Rift system. The Luangwa River and major tributaries, such as the Luwumbu River, are perennial water sources supporting essential resources that sustain human communities and a rich and diverse fauna and flora. The archaeological record of Luangwa is relatively unknown, despite early archaeological exploration hinting at its potential. Recent research in the southern Luangwa valley, however, suggests that it preserves a long record of hominin occupation spanning the Early to Late Stone Age. The research described here details fieldwork carried out in northeastern Luangwa, in the Luwumbu Basin, that confirms that a relatively deep package of Quaternary deposits, containing evidence of the Stone Age occupation of the region persists in the upper piedmont zone.

Using Real-world Data to Define a Validated Nomogram for Advanced Bladder Cancer Patients Who Respond to Immunotherapy.

AIMS: Immune checkpoint inhibitors (ICIs) are used in incurable urothelial cancers, both in chemo-naïve and platinum-refractory patients. Efficacy and toxicity data published outside controlled clinical trials are limited. We report overall survival, progression-free survival and toxicities of ICIs in locally advanced (LABC) or metastatic bladder cancer (MBC). We aimed to develop and validate a prognostic model for these patients. MATERIALS AND METHODS: A multicentre real-world individual patient-level data study (n = 272) evaluating ICIs in the first-line platinum-ineligible or platinum-refractory setting for LABC/MBC between March 2017 and February 2020 was undertaken. Cox regression analyses evaluated the association of prognostic factors with overall survival. Data were split to create a training (n = 208) and validation (n = 64) cohort. The backward elimination method with a P-value cut-off of 0.05 was used to develop a reduced prognostic model using the training data set. The concordance index and assessment of observed versus predicted survival probabilities were used to evaluate the final model. RESULTS: The median follow-up was 18.9 (15.8-21.5) months. The median overall survival and progression-free survival in the training cohort were 9.2 (95% confidence interval 7.4-10.5) and 4.5 months (3.5-5.7), respectively. The most common grade 1/2 adverse events recorded were fatigue (47.8%) and infection (19.9%). Five key prognostic factors found in the training set were low haemoglobin, high neutrophil count, choice of immunotherapy favouring pembrolizumab, presence of liver metastasis and steroid use within 30 days of treatment. The concordance index for the training and validation cohorts was 0.66 (standard error = 0.05) and 0.64 (standard error = 0.04), respectively, for the final model. A nomogram was developed to calculate the expected survival probabilities based on risk factors. CONCLUSIONS: Real-world data were used to produce a validated prognostic model for overall survival in LABC/MBC treated with ICIs. This model could assist in patient stratification, interpreting and framing future trials incorporating PD-1/PD-L1 inhibitors in LABC/MBC.

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.

BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. METHODS: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. RESULTS: Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). CONCLUSIONS: The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

An introduction to patient-reported outcome measures (PROMs) in physiotherapy.

The use of patient-reported outcome measures (PROMs) is set to rise in physiotherapy. PROMs provide additional 'patient-centred' data which is unique in capturing the patient's own opinion on the impact of their disease or disorder, and its treatment, on their life. Thus, PROMs are increasingly used by clinicians to guide routine patient care, or for the purposes of audit, and are already firmly embedded in clinical research. This article seeks to summarise the key aspects of PROM use for physiotherapists, both in routine clinical practice and in the research setting, and highlights recent developments in the field. Generic and condition-specific PROMs are defined and examples of commonly used measures are provided. The selection of appropriate PROMs, and their effective use in the clinical and research settings is discussed. Finally, existing barriers to PROM use in practice are identified and recent physiotherapy PROM initiatives, led by the Royal Dutch Society for Physical Therapy are explored.

Fibromatosis: benign by name but not necessarily by nature.

Aggressive fibromatoses, also known as desmoid tumours, are rare fibrous tissue proliferations with a tendency for slow, local infiltrative growth. There is an association with Gardner's syndrome and familial adenomatous polyposis. Histologically they are fairly bland with no abnormal mitoses or necrosis. They do not metastasize, but can cause significant morbidity through their locally destructive effects. Magnetic resonance imaging is the method of choice for diagnosis, pre-treatment planning and post-treatment follow-up. Surgical excision with a wide margin is the treatment of choice. However, there is a tendency for local recurrence and repeated excision may result in a poor functional or cosmetic outcome. Radiotherapy is used to reduce local recurrence rates after excision and is also used to treat inoperable tumours. Long-lasting remissions can be obtained. Treatment is now planned using modern three-dimensional conformal techniques, similar to those used in soft tissue sarcoma management. There is no definite dose-response relationship, but doses of 50-60 Gy in 1.8-2 Gy fractions are recommended. Systemic therapy has been used for lesions not controlled by surgery or radiotherapy, or less commonly, as a primary treatment. Tamoxifen and non-steroidal anti-inflammatory agents are used most often as they are relatively non-toxic, but there is limited experience with cytotoxic chemotherapy and biological agents. There are no randomised trials to help guide the management of this locally aggressive 'benign' tumour and treatment decisions are best made by the local soft tissue sarcoma multidisciplinary team.

Late toxicity after short course preoperative radiotherapy and total mesorectal excision for resectable rectal cancer.

AIMS: The late toxicity of short-course preoperative radiotherapy (SCPRT) after total mesorectal excision (TME) in resectable rectal cancer has not been adequately documented. The acute toxicity in a series of 176 consecutive patients has been previously reported. In this study, the late toxicity in the same cohort is presented. MATERIALS AND METHODS: Side-effects occurring more than 3 months after the start of SCPRT were graded using the EORTC/RTOG late radiation toxicity system. We performed multivariate analysis to identify associated factors. RESULTS: Of 176 patients, 15 died within 3 months of SCPRT and five patients were lost to follow-up. One hundred and fifty-six patients were assessable at a median follow-up interval of 41 months: severe (grade 3-4) toxicity was seen in 20 patients (13%), of which 13 were gastrointestinal (8%); three urological (2%); three thromboembolic (2%), and one musculoskeletal (1%). On multivariate analysis, abdomino-perineal (AP) resection (P < 0.02) was associated with a lower risk of grade 3-4 toxicity. CONCLUSIONS: In this retrospective study, the rate of late grade 3-4 toxicity after SCPRT and TME was 13%. Although AP resection seems to be associated with a lower incidence of late toxicity, this could be counterbalanced by the impact of a stoma on quality of life. These factors should be considered when determining the optimal management of resectable rectal cancers.