journal article
LitStream Collection
Home
Elwood, Peter; Morgan, Gareth; Watkins, John; Protty, Majd; Mason, Malcolm; Adams, Richard; Dolwani, Sunil; Pickering, Janet; Delon, Christine; Longley, Marcus
doi: 10.1038/s41416-023-02506-5pmid: 38030748
Aspirin as a possible treatment of cancer has been of increasing interest for over 50 years, but the balance of the risks and benefits remains a point of contention. We summarise the valid published evidence ‘for’ and ‘against’ the use of aspirin as a cancer treatment and we present what we believe are relevant ethical implications. Reasons for aspirin include the benefits of aspirin taken by patients with cancer upon relevant biological cancer mechanisms. These explain the observed reductions in metastatic cancer and vascular complications in cancer patients. Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use. Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding. Few trials have been reported and there are inconsistencies in the results. In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence and encouraged to raise the topic with their healthcare team.
Clements, Hollie A.; Underwood, Tim J.; Petty, Russell D.
doi: 10.1038/s41416-023-02458-wpmid: 37898721
Adenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery. In this review, we discuss the current evidence for total neoadjuvant therapy and options for assessment of treatment response.[graphic not available: see fulltext]
Wardill, Hannah R.; Wooley, Luke T.; Bellas, Olivia M.; Cao, Katrina; Cross, Courtney B.; van Dyk, Madele; Kichenadasse, Ganessan; Bowen, Joanne M.; Zannettino, Andrew C. W.; Shakib, Sepehr; Crawford, Gregory B.; Boublik, Jaroslav; Davis, Mellar M.; Smid, Scott D.; Price, Timothy J.
Jo, Jung Hyun; Kim, Yong-Tae; Choi, Ho Soon; Kim, Ho Gak; Lee, Hong Sik; Choi, Young Woo; Kim, Dong Uk; Lee, Kwang Hyuck; Kim, Eui Joo; Han, Joung-Ho; Lee, Seung Ok; Park, Chang-Hwan; Choi, Eun Kwang; Kim, Jae Woo; Cho, Jae Yong; Lee, Woo Jin; Moon, Hyungsik Roger; Park, Mi-Suk; Kim, Sangjae;
Zhao, Jimmy L.; Antonarakis, Emmanuel S.; Cheng, Heather H.; George, Daniel J.; Aggarwal, Rahul; Riedel, Elyn; Sumiyoshi, Takayuki; Schonhoft, Joseph D.; Anderson, Amanda; Mao, Ninghui; Haywood, Samuel; Decker, Brooke; Curley, Tracy; Abida, Wassim;
Eslami-S, Zahra; Cortés-Hernández, Luis Enrique; Sinoquet, Léa; Gauthier, Ludovic; Vautrot, Valentin; Cayrefourcq, Laure; Avoscan, Laure; Jacot, William; Pouderoux, Stéphane; Viala, Marie; Thomas, Quentin Dominique; Lamy, Pierre-Jean; Quantin, Xavier; Gobbo, Jessica; Alix-Panabières, Catherine
Shen, John; Chowdhury, Simon; Agarwal, Neeraj; Karsh, Lawrence I.; Oudard, Stéphane; Gartrell, Benjamin A.; Feyerabend, Susan; Saad, Fred; Pieczonka, Christopher M.; Chi, Kim N.; Brookman-May, Sabine D.; Rooney, Brendan; Bhaumik, Amitabha; McCarthy, Sharon A.; Bevans, Katherine B.; Mundle, Suneel D.; Small, Eric J.; Smith, Matthew R.;
Park, Yikyung; Farhat, Zeinab; Liao, Linda M.; Inoue-Choi, Maki; Loftfield, Erikka
doi: 10.1038/s41416-023-02421-9pmid: 38017130
BackgroundDespite no sufficient evidence on benefits and harms of multivitamin use, cancer survivors use multivitamins as a self-care strategy to improve or maintain health. We examined if multivitamin use was associated with mortality in cancer survivors.Methods15,936 male and 7026 female cancer survivors in the NIH-AARP Diet and Health Study were included in the analysis. Types and frequency of multivitamin use at on average 4.6 years after cancer diagnosis were assessed. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models.ResultsMultivitamin use was not associated with lower all-cause mortality risk in all female (RR = 0.94, 95% CI:0.87–1.01 daily vs. no use) or male cancer survivors (RR = 0.96, 95% CI:0.91–1.00); however, a modest inverse association for CVD mortality was observed in female survivors of reproductive cancers (RR = 0.75, 95% CI:0.61–0.92) and male survivors of non-reproductive cancers (RR = 0.81, 95% CI:0.70–0.94). Multivitamin use was also associated with a lower risk of cancer-specific mortality in survivors of skin (RR = 0.65, 95% CI:0.48–0.88) and breast (RR = 0.79, 95% CI:0.65–0.95) cancer.DiscussionMultivitamin use may provide a modest survival benefit to some cancer survivors. Cancer care providers should talk with cancer survivors about potential benefits and harms of multivitamin use.[graphic not available: see fulltext]
Showing 1 to 10 of 19 Articles
The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.
BackgroundThe tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear.MethodsWe conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining.ResultsPatients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN.ConclusionEnlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.[graphic not available: see fulltext]
doi: 10.1038/s41416-023-02474-wpmid: 37903909
BackgroundThe TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC.MethodsPatients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2–4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety.ResultsTotal 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively.ConclusionsGV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC.Clinical trial registrationNCT02854072.
doi: 10.1038/s41416-023-02487-5pmid: 37980367
BackgroundCC-115, a dual mTORC1/2 and DNA-PK inhibitor, has promising antitumour activity when combined with androgen receptor (AR) inhibition in pre-clinical models.MethodsPhase 1b multicentre trial evaluating enzalutamide with escalating doses of CC-115 in AR inhibitor-naive mCRPC patients (n = 41). Primary endpoints were safety and RP2D. Secondary endpoints included PSA response, time-to-PSA progression, and radiographic progression.ResultsCommon adverse effects included rash (31.7% Grades 1–2 (Gr); 31.7% Gr 3), pruritis (43.9% Gr 1–2), diarrhoea (37% Gr 1–2), and hypertension (17% Gr 1–2; 9.8% Gr 3). CC-115 RP2D was 5 mg twice a day. In 40 evaluable patients, 80% achieved ≥50% reduction in PSA (PSA50), and 58% achieved ≥90% reduction in PSA (PSA90) by 12 weeks. Median time-to-PSA progression was 14.7 months and median rPFS was 22.1 months. Stratification by PI3K alterations demonstrated a non-statistically significant trend towards improved PSA50 response (PSA50 of 94% vs. 67%, p = 0.08). Exploratory pre-clinical analysis suggested CC-115 inhibited mTOR pathway strongly, but may be insufficient to inhibit DNA-PK at RP2D.ConclusionsThe combination of enzalutamide and CC-115 was well tolerated. A non-statistically significant trend towards improved PSA response was observed in patients harbouring PI3K pathway alterations, suggesting potential predictive biomarkers of response to a PI3K/AKT/mTOR pathway inhibitor.Clinical trial registrationClinicalTrials.gov identifier: NCT02833883.
doi: 10.1038/s41416-023-02491-9pmid: 37973956
BackgroundCirculating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients.MethodsPlasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay.ResultsAt least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57–1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03–1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99–1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11–18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001).ConclusionCTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS.Trial registrationNCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149.
doi: 10.1038/s41416-023-02492-8pmid: 37951974
BackgroundApalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment.MethodsPost-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures.ResultsHazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40–0.80), 0.70 (0.54–0.91) and 0.74 (0.40–1.39) (TITAN) and 0.39 (0.19–0.78), 0.89 (0.69–1.16) and 0.81 (0.58–1.15) (SPARTAN) in patients aged <65, 65–79 and ≥80 years. Regardless of age, apalutamide also maintained HRQoL and was tolerated well with a potential trend in rates of adverse events increasing with age. Limitations include post-hoc nature and variability in sample size of age groups.ConclusionsApalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of age.Clinical trial registrationTITAN (NCT02489318); SPARTAN (NCT01946204).