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A randomized trial showed noninferiority of stereotactic body radiotherapy to conventionally or moderately hypofractionated radiotherapy in preventing biochemical recurrence in selected men with localized prostate cancer.

Current controversies about rectal cancer treatment are examined and discussed in this book. In particular, oncologic outcomes, which claim an aggressive approach over the primary tumour, lymph nodes and distant metastasis. Also, the functional outcome, whose important objective is to preserve the anal sphincter and the preservation of the pelvic nervous plexus. Radical resection with total mesorectal excision is the mainstay of rectal cancer treatment. However, it is associated with significant surgical morbidity/mortality, possible stoma surgery/complications and long-term gastrointestinal dysfunction with deterioration in quality of life. This book also explores the risk factors of local recurrence after curative resection in patients with middle and lower rectal carcinoma. The relationships between mesorectal metastasis and local recurrence and the possible correlations between circumferential resection margin status and local recurrence were identified. The relationships between local recurrence and clinicopathologic characteristics of middle and lower rectal carcinoma were also evaluated.

Introduction We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient non‐squamous non‐small cell lung cancer (NSCLC) via a phase 1 dose‐expansion trial with exploratory biomarker analysis. Methods Sixty‐seven chemonaïve patients with advanced non‐squamous NSCLC were screened, enrolling 21 ASS1‐deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36 mg/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry. Results ADIPemCis was well‐tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n = 18/21; 95% CI 63.7%–97%), with a partial response rate of 47.6% (n = 10/21; 95% CI 25.7%–70.2%). The median progression‐free and overall survivals were 4.2 (95% CI 2.9–4.8) and 7.2 (95% CI 5.1–18.4) months, respectively. Two PD‐L1‐expressing (≥1%) patients are alive following subsequent pembrolizumab immunotherapy (9.5%). Tumoral ASS1 deficiency enriched for p53 (64.7%) mutations, and numerically worse median overall survival as compared to ASS1‐proficient disease (10.2 months; n = 29). There was no apparent increase in KRAS mutations (35.3%) and PD‐L1 (<1%) expression (55.6%). Re‐expression of tumoral ASS1 was detected in one patient at progression (n = 1/3). Conclusions ADIPemCis was safe and highly active in patients with ASS1‐deficient non‐squamous NSCLC, however, survival was poor overall. ASS1 loss was co‐associated with p53 mutations. Therapies incorporating pegargiminase merit further evaluation in ASS1‐deficient and treatment‐refractory NSCLC. We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient non‐squamous non‐small cell lung cancer (NSCLC) via a phase 1 dose‐expansion trial with exploratory biomarker analysis. ADIPemCis was safe and highly active in patients with ASS1‐deficient non‐squamous NSCLC, however, survival was poor overall. ASS1 loss was co‐associated with p53 mutations providing a developmental pathway for further testing pegargiminase in ASS1‐deficient and treatment‐refractory NSCLC.

Part 1 of this article highlighted the potential negative effects of cancer on the skeleton and provided an overview of available treatment options. Part 2 presents a nurse practitioner-led Bone Support Clinic, which was developed for patients with cancer-induced bone disease and cancer therapy-induced bone loss. This clinic, started in 2011 in a university medical center urology/oncology outpatient center in London, England, United Kingdom, has been a collaborative effort among a multidisciplinary team of doctors, nurse practitioners and nurses. Patients have responded positively to the improved continuity of care, and we have been able to assess and treat impending skeletal-related events in a more timely manner The needs of our patient population and problems with the existing service are reviewed, and the importance of a multidisciplinary approach to these problems is discussed. Initiation of a nurse practitioner-led Bone Support Clinic and the impact of timely response to the effects of cancer and cancer therapies on the skeletal system are outlined and offered as a model.

Moderately hypofractionated radiotherapy (MHRT) is a standard treatment for prostate cancer. Stereotactic body radiotherapy (SBRT) is also effective, and has been shown to be non-inferior to MHRT in a lower-risk group of patients who did not require hormone therapy (PACE-B), but randomised data on toxicity for higher-risk patients are lacking. We aimed to compare the early toxicity of MHRT and SBRT. The randomised, open-label, phase 3, non-inferiority PACE-C trial, conducted at 53 hospitals across the UK, Republic of Ireland, and New Zealand, recruited men aged at least 18 years with intermediate-risk or high-risk histologically confirmed prostate adenocarcinoma (T1–T3a, Gleason 7–8, and prostate specific antigen 10–30 ng/mL) and with WHO performance status of 0–2. Participants were centrally randomly assigned (1:1; non-masked; permuted block size of four and six; stratified by centre and risk group) to MHRT (60 Gy; 20 daily fractions over 4 weeks) or SBRT (36·25 Gy; five daily or alternate day fractions; over 1–2 weeks) with an additional mandatory clinical target volume dose target of 40 Gy (no margin) to the prostate, and proximal 1 cm of seminal vesicles. 6 months of androgen deprivation therapy was planned and was started before commencement of radiotherapy. The primary outcome of PACE-C is freedom from biochemical or clinical failure, the data for which are not yet mature. The co-primary endpoints for this preplanned safety analysis were the percentages of Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicities at any point during or within 12 weeks of completion of radiotherapy (the early or acute period). Analyses are by treatment received, with participants included if they had one or more fractions of MHRT or SBRT, regardless of their allocated treatment. Late toxicity and efficacy data are awaited as the trial remains in follow-up. The study was prospectively registered with ClinicalTrials.gov, NCT01584258. Between Nov 13, 2019, and June 24, 2022, 1208 participants were randomly assigned (601 to MHRT and 607 to SBRT). 608 patients received MHRT and 584 received SBRT, and thus were included in the study analysis. 1136 (95%) of 1192 patients were White, 20 (2%) were Black or Black British, 17 (1%) were Asian or Asian British, and seven (1%) were Chinese or other. During the early period (within 12 weeks of treatment), the co-primary endpoint of RTOG grade 2 or worse genitourinary toxicity was observed in 166 (27%) of 608 patients (95% CI 23·8 to 31·1) receiving MHRT and 162 (28%) of 582 patients (24·3 to 31·7) after SBRT (absolute difference 0·5%, 95% CI –4·7 to 5·7; p=0·89). For grade 2 or worse genitourinary Common Terminology Criteria for Adverse Events (CTCAE), 170 (28%) of 604 patients had events after MHRT and 195 (34%) of 581 patients had events after SBRT (p=0·050). Grade 3 CTCAE genitourinary toxicity was observed in three (<1%) patients receiving MHRT and three (1%) patients receiving SBRT. For grade 2 or worse gastrointestinal CTCAE, 60 (10%) of 604 patients had an event after MHRT and 96 (17%) of 581 patients had an event after SBRT (p=0·0011). Grade 3 CTCAE gastrointestinal toxicity was observed in three (<1%) patients receiving MHRT and four (1%) patients receiving SBRT. During the early period, the co-primary endpoint of RTOG grade 2 or worse gastrointestinal toxicity was observed in 69 (11%) of 608 patients (95% CI 9·0 to 14·2) receiving MHRT and 74 (13%) of 584 patients (10·2 to 15·8) receiving SBRT (absolute difference 1·4%, 95% CI –2·5 to 5·2; p=0·53). There were no treatment-related deaths. Despite an accelerated treatment schedule and a larger treated volume than PACE-B, SBRT and MHRT had similar rates of early RTOG toxicity. The Royal Marsden Cancer Charity.

The COVID-19 pandemic has necessitated adaptation of cancer patient care. Oncology patients who contract COVID-19 have poor outcomes. Telemedicine clinics (teleclinics) have been introduced for cancer patients to reduce the risk of horizontal transmission at St. Bartholomew’s Hospital and The Royal Free Hospital in London. Teleclinics have become routine in many specialities; however, inclusion in oncology care was not standard prior to the pandemic. A mixed-methods survey was designed and delivered to cancer patients (n = 106) at St. Bartholomew’s Hospital and The Royal Free Hospital who had transitioned to teleclinics in March 2020. The survey explored patients’ perceptions of this format. In total, 96 (90.5%) patients consented to take part, across a range of tumour types. Overall, respondents reacted favourably to the format of the teleclinics, with 90.6% of respondents (87/96) stating they would utilise teleclinics beyond the pandemic. Additionally, a survey was distributed to clinicians delivering these teleclinics (n = 16) to explore previous training in, perceptions of, and lessons learned from the introduction of telemedicine. Results suggest patients are accepting of teleclinic use for most clinical purposes. Teleclinic implementation affords benefits to cancer patient care both during and after COVID-19, but there is an urgent need for telemedicine education in oncology specialty training.

The aim of this study was to investigate the feasibility of evaluating the pharmacokinetics of radiolabeled anti-cancer drugs using spectral analysis, a non-compartmental tracer kinetic modeling technique, and positron emission tomography (PET). Dynamic PET studies were performed on patients receiving tracer doses of 5-fluorouracil (5-[18F]-FU) and two developmental drugs [11C]-temozolomide and [11C]-acridine carboxamide. Spectral analysis was then used to (a) determine individual and group average pharmacokinetics, (b) predict tumour handling in response to different drug administration regimens, and (c) produce functional parametric images describing regional pharmacokinetics. Spectral analysis could distinguish tumour kinetics from normal tissue kinetics in an individual [11C]-temozolomide study and demonstrated a markedly greater volume of distribution (VD) in glioma than in normal brain, although there was no appreciable difference in mean residence time. Analysis of pooled acridine carboxamide data (n = 22) revealed a relatively large VD (and prolonged retention) in the liver and spleen and a markedly lower VD (and initial uptake) in the brain. Continuous infusion of 5-[18F]-FU was predicted to achieve a concentration in colorectal metastases in liver approximately 10 times that achieved in plasma at 10 h after commencement of the infusion. We conclude that spectral analysis provides important pharmacokinetic information about radiolabeled anti-cancer drugs with relatively few model assumptions.