Stellar clustering shapes the architectures of planetary systems

Planet formation is generally described in terms of a system containing the host star and a protoplanetary disc, of which the internal properties (e.g. mass and metallicity) determine the properties of the resulting planetary system. However, (proto)planetary systems are predicted and observed to be affected by the spatially-clustered stellar formation environment, either through dynamical star-star interactions or external photoevaporation by nearby massive stars. It is challenging to quantify how the architecture of planetary systems is affected by these environmental processes, because stellar groups spatially disperse within <1 billion years, well below the ages of most known exoplanets. Here we identify old, co-moving stellar groups around exoplanet host stars in the astrometric data from the Gaia satellite and demonstrate that the architecture of planetary systems exhibits a strong dependence on local stellar clustering in position-velocity phase space, implying a dependence on their formation or evolution environment. After controlling for host stellar age, mass, metallicity, and distance from the Sun, we obtain highly significant differences (with $p$-values of $10^{-5}{-}10^{-2}$) in planetary (system) properties between phase space overdensities and the field. The median semi-major axis and orbital period of planets in overdensities are 0.087 au and 9.6 days, respectively, compared to 0.81 au and 154 days for planets around field stars. 'Hot Jupiters' (massive, close-in planets) predominantly exist in stellar phase space overdensities, strongly suggesting that their extreme orbits originate from environmental perturbations rather than internal migration or planet-planet scattering. Our findings reveal that stellar clustering is a key factor setting the architectures of planetary systems

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Ultrassom anorretal tri-dimensional pode selecionar pacientes com tumor no reto após neoadjuvância para cirurgia de preservação esfincteriana? Can three-dimensional anorectal ultrasound select patients with rectal tumor for sphincter-saving resection after post-chemoradiotherapy

OBJETIVO: Avaliar a resposta pós-quimioradioterapia-QT no tratamento do tumor no reto utilizando ultrassom anorretal tridimensional(US-3-D) visando definir a estratégia cirúrgica adequada. MÉTODO: Avaliou-se prospectivamente 32 pacientes com adenocarcinoma no reto médio e inferior. Realizou-se US-3-D para estadiamento e avaliação quanto à invasão no canal anal ou distância(cm) entre tumor e esfíncter anal interno-EAI: GrupoI-invasão no canal anal; GrupoII-distância menor-ou-igual 2cm, GrupoIII-distância maior 2. Foram encaminhados neoadjuvância e realizado US-3D após 50-55 dias. A escolha da estratégia cirúrgica baseou-se na resposta pós-QT e achados do US-3-D/pós-QT e comparado com histopatológico. RESULTADOS: O US-3-D/pós-QT coincidiu com histopatológico em 31/32, eficácia de 97%. Evidenciou-se 26/27 casos com lesão residual, sensibilidade de 96%, sendo 19(59%) resposta parcial e 07 (22%) sem resposta. Em 5/5 o US-3-D/pós-QT demonstrou resposta completa, especificidade e valor preditivo positivo 100%. Valor preditivo negativo 83% pois um(3%) caso inconclusivo. Realizou-se cirurgia de preservação esfincteriana em 16 pacientes (05 com resposta completa, 10 com resposta parcial e um inconclusivo) com margem maior que 2cm. Confirmados ao histopatológico com margem livre. O índice Kappa na avaliação de linfonodos demonstrou concordância substancial(87,5%). Conclui-se que o US-3D pode ser útil na escolha de pacientes que irão beneficiar-se com a cirurgia de preservação esfincteriana.<br>PROPOSAL: Evaluate the post-chemoradiotherapy response for treatment of rectal tumor using three-dimensional anorectal ultrasound-3D-US to determine the best surgical approach METHODS: 32 patients with lower and middle rectal cancer were prospectively staged using 3D-US to identify anal canal invasion and the distance(cm) between tumor and the internal anal sphincter-IAS, Group l:with anal canal invasion; Group II-with distance =2cm; Group III-with distance >2. They were submitted to neoadjuvant chemoradiation-CRT and the 3-D US was repeated 50-55 days later. The choice of the surgical approach was based on the post-chemoradiation response identified by the 3D-US comparing with pathologic findings. RESULTS: The post-chemoradiation/3D-US findings were concordant with pathologic results in 31/32(97%). It was identified residual tumors in 26/27(96% sensibility), 19(59%) with partial response and 7(22%) without response. Complete response was demonstrated in 5/5 by 3D-US, with specificity and predictive valor in 100%. Negative predictive valor in 83% since one(3%) case was inconclusive. Sphincter-saving resection was performed in 16 patients, 5 with complete response, 10 with partial response and one inconclusive, with distal margin >2cm. The pathologic findings confirmed distal margins without tumor. It was demonstrated high concordance(87.5%) concerning the lymph nodes evaluation(Kappa test). CONCLUSION: 3D-US can be useful to determine the patients who should be submitted to sphincter-saving resections

Changing outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer

Background Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time. Methods This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Surgical outcomes, including rate of bone resection, flap reconstruction, margin status and transfusion rates, were examined. Outcomes between higher- and lower-volume centres were also evaluated. Results Some 2472 patients underwent pelvic exenteration for LARC and LRRC across 26 institutions. For LARC, rates of bone resection or flap reconstruction increased from 2004 to 2015, from 3.5 to 12.8 per cent, and from 12.0 to 29.4 per cent respectively. Fewer units of intraoperative blood were transfused over this interval (median 4 to 2 units; P = 0.040). Subgroup analysis showed that bone resection and flap reconstruction rates increased in lower- and higher-volume centres. R0 resection rates significantly increased in low-volume centres but not in high-volume centres over time (low-volume: from 62.5 to 80.0 per cent, P = 0.001; high-volume: from 83.5 to 88.4 per cent, P = 0.660). For LRRC, no significant trends over time were observed for bone resection or flap reconstruction rates. The median number of units of intraoperative blood transfused decreased from 5 to 2.5 units (P &lt; 0.001). R0 resection rates did not increase in either low-volume (from 51.7 to 60.4 per cent; P = 0.610) or higher-volume (from 48.6 to 65.5 per cent; P = 0.100) centres. No significant differences in length of hospital stay, 30-day complication, reintervention or mortality rates were observed over time. Conclusion Radical resection, bone resection and flap reconstruction rates were performed more frequently over time, while transfusion requirements decreased

Palliative pelvic exenteration: A systematic review of patient-centered outcomes

Objective: Palliative pelvic exenteration (PPE) is a technically complex operation with high morbidity and mortality rates, considered in patients with limited life expectancy. There is little evidence to guide practice. We performed a systematic review to evaluate the impact of PPE on symptom relief and quality of life (QoL). Methods: A systematic review was conducted according to the PRISMA guidelines using Ovid MEDLINE, EMBASe, and PubMed databases for studies reporting on outcomes of PPE for symptom relief or QoL. Descriptive statistics were used on pooled patient cohorts. Results: Twenty-three historical cohorts and case series were included, comprising 509 patients. No comparative studies were found. Most malignancies were of colorectal, gynaecological and urological origin. Common indications for PPE were pain, symptomatic fistula, bleeding, malodour, obstruction and pelvic sepsis. The pooled median postoperative morbidity rate was 53.6% (13–100%), the median in-hospital mortality was 6.3% (0–66.7%), and median OS was 14 months (4–40 months). Some symptom relief was reported in a median of 79% (50–100%) of the patients, although the magnitude of effect was poorly measured. Data for QoL measures were inconclusive. Five studies discouraged performing PPE in any patient, while 18 studies concluded that the procedure can be considered in highly selected patients. Conclusion: Available evidence on PPE is of low-quality. Morbidity and mortality rates are high with a short median OS interval. While some symptom relief may be afforded by this procedure, evidence for improvement in QoL is limited. A highly selective individualised approach is required to optimise the risk:benefit equation

Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative

Aim At presentation, 15-20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection.Method Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival.Results Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006).Conclusion Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated