Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer – A multicentre dose planning study

Background and purpose Organ preservation strategies are increasingly being explored for early rectal cancer. This requires revision of target volumes according to disease stage, as well as new guidelines for treatment planning. We conducted an international, multicentre dose planning study to develop robust planning objectives for modern radiotherapy of a novel mesorectal-only target volume, as implemented in the STAR-TReC trial (NCT02945566). Materials and methods The published literature was used to establish relevant dose levels for organ at risk (OAR) plan optimisation. Ten representative patients with early rectal cancer were identified. Treatment scans had mesorectal target volumes as well as bowel cavity, bladder and femoral heads outlined, and were circulated amongst the three participating institutions. Each institution produced plans for short course (SCRT, 5 × 5 Gy) and long course (LCRT, 25 × 2 Gy) treatment, using volumetric modulated arc therapy on different dose planning systems. Optimisation objectives for OARs were established by determining dose metric objectives achievable for ≥90% of plans. Results Sixty plans, all fulfilling target coverage criteria, were produced. The planning results and literature review suggested optimisation objectives for SCRT: V10Gy < 180 cm3, V18Gy < 110 cm3, V23Gy < 85 cm3 for bowel cavity; V21Gy < 15% and V25Gy < 5% for bladder; and V12.5Gy < 11% for femoral heads. Corresponding objectives for LCRT: V20Gy < 180 cm3, V30Gy < 130 cm3, V45Gy < 90 cm3 for bowel cavity; V35Gy < 22% and V50Gy < 7% for bladder; and V25Gy < 15% for femoral heads. Constraints were validated across all three institutions. Conclusion We utilized a multicentre planning study approach to develop robust planning objectives for mesorectal radiotherapy for early rectal cancer

A Machine-Learning-Based Bibliometric Analysis of the Scientific Literature on Anal Cancer

Squamous-cell carcinoma of the anus (ASCC) is a rare disease. Barriers have been encountered to conduct clinical and translational research in this setting. Despite this, ASCC has been a prime example of collaboration amongst researchers. We performed a bibliometric analysis of ASCC-related literature of the last 20 years, exploring common patterns in research, tracking collaboration and identifying gaps. The electronic Scopus database was searched using the keywords “anal cancer”, to include manuscripts published in English, between 2000 and 2020. Data analysis was performed using R-Studio 0.98.1091 software. A machine-learning bibliometric method was applied. The bibliometrix R package was used. A total of 2322 scientific documents was found. The average annual growth rate in publication was around 40% during 2000–2020. The five most productive countries were United States of America (USA), United Kingdom (UK), France, Italy and Australia. The USA and UK had the greatest link strength of international collaboration (22.6% and 19.0%). Two main clusters of keywords for published research were identified: (a) prevention and screening and (b) overall management. Emerging topics included imaging, biomarkers and patient-reported outcomes. Further efforts are required to increase collaboration and funding to sustain future research in the setting of ASCC

mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.National Institutes of Health (U.S.) (CA103866)National Institutes of Health (U.S.) (CA129105)David H. Koch Institute for Integrative Cancer Research at MIT (Initiator Award)Ellison Medical FoundationNational Cancer Institute (U.S.) (NCI (T32CA09216) fellowship support)Academy of FinlandFoundations’ Postdoc PoolNational Institutes of Health (U.S.) (NIH (1F32AG032833-01A1))Jane Coffin Childs Memorial Fund for Medical Researc

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Re-RAD-I external beam radiotherapy for pelvic recurrences in rectal cancer patients previously treated with radiotherapy

Background: Multimodal treatment of rectal cancer has improved outcome, but some patients still experience local recurrence, which is a major therapeutic challenge after previous radiotherapy (RT). Re-irradiation may improve the rate of radical surgery (R0), as reported in previous studies, where hyperfractionated chemo-RT resulted in 35% R0 rate. Surgery, RT techniques, and imaging have improved recent years, allowing for increased treatment precision with less morbidity. This study investigates re-irradiation of patients with local recurrence in a phase II clinical, imaging and translational study. Trial design: A prospective multicenter phase II, open label, non-randomised study. Therapy: External beam RT of 40.8 Gy / 1.2 F BID by intensity-modulated RT + CBCT guidance, concomitant capecitabine 825 mg/m2 BID all RT days, and surgery 8 weeks post-RT. The primary endpoint is R0 rate. Secondary objectives: Recurrence-free, disease-free and overall survival, acute and late toxicity, patient reported outcomes, translational research, imaging studies for future adaptive RT, mapping of recurrences according to previous RT, and simulation studies of other RT modalities (proton therapy). Main inclusion criteria: Locally recurrent rectal cancer, previous pelvic RT and surgery, potentially resectable tumor, age ≥18 years, adequate organ function, acceptable bowel and bladder function, acceptance for translational research. Main exclusion criteria; central small recurrences deemed resectable, non-resectable distant metastases, medical comorbidities precluding radical surgery, previous RT <12 months prior to recurrence, unability for MRI or PET-CT. Statistics; Simons two-stage design, with expected R0 of 30% by ITT and expected R0 increase to 45%, σ = 0:05; 1 − β= 0:8. Total sample size is 65 patients. Centers in Denmark and Norway are currently recruiting

Treatment of Squamous Cell Carcinoma of the Anus, Unresolved Areas and Future Perspectives for Research: Perspectives of Research Needs in Anal Cancer

Anal cancer is a relatively rare, mostly HPV-related cancer. The curative treatment consists of concurrent chemoradiation delivered with modern radiotherapy techniques. The prognosis for most patients with early localized disease is very favourable; however patients with locally advanced disease and/or HPV negative tumours are at higher risk of locoregional and distant treatment failure. Tailored approaches are presently being investigated to determine the most suitable regimen in terms of radiotherapy dose prescription, target volume selection, normal tissue avoidance, and combination therapy. Metastatic anal cancer is treated with chemotherapy aiming at prolonged survival. The role of immune therapy in the clinical setting is being investigated. There is little knowledge on the biology of anal cancer, and an urgent need for more clinical and translational research dedicated to this disease. In this article, the evidence-base for the current treatment is briefly reviewed, and perspectives on future research needs are high-lighted

International expert consensus statement regarding radiotherapy treatment options for rectal cancer during the COVID 19 pandemic

The rapid spread of COVID19 infection across the globe is causing a health care emergency. Our aim is to assist discussion about the risks and benefits to facilitate decision-making regarding radiotherapy for rectal cancer patients. In our roles as clinicians and as experts who have conducted clinical trials evaluating the role of radiotherapy in rectal cancer, we present our assessment of treatment options that should be considered by health care professionals in the setting of the COVID 19 pandemic. We want to minimize the risks to our patients whilst aiming to maintain cancer outcomes. We have used the European Society for Medical Oncology (ESMO) rectal cancer guidelines as a framework to describe our recommendation