Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours.

BACKGROUND: MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT. METHODS: We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations. CONCLUSIONS: MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.

Prostate cancer patient-derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens.

Patient-derived organoids (PDOs) represent promising preclinical models in various tumor types. In the context of prostate cancer (PCa), however, their establishment has been hampered by poor success rates, which impedes their broad use for translational research applications. Along with the necessity to improve culture conditions, there is a need to identify factors influencing outcomes and to determine how to assess success versus failure in organoid generation. In the present study, we report our unbiased efforts to generate PDOs from a cohort of 81 PCa specimens with diverse pathological and clinical features. We comprehensively analyzed histological features of each enrolled sample (Gleason score, tumor content, proliferation index) and correlated them with organoid growth patterns. We identified improved culture conditions favoring the generation of PCa organoids, yet no specific intrinsic tumor feature was broadly associated with sustained organoid growth. In addition, we performed phenotypic and molecular characterization of tumor-organoid pairs using immunohistochemistry, immunofluorescence, fluorescence in situ hybridization, and targeted sequencing. Morphological and immunohistochemical profiles of whole organoids altogether provided a fast readout to identify the most promising ones. Notably, primary samples were associated with an initial take-rate of 83% (n = 60/72) in culture, with maintenance of cancer cells displaying common PCa alterations, such as PTEN loss and ERG overexpression. These cancer organoids were, however, progressively overgrown by organoids with a benign-like phenotype. Finally, out of nine metastasis samples, we generated a novel organoid model derived from a hormone-naïve lung metastasis, which displays alterations in the PI3K/Akt and Wnt/ß-catenin pathways and responds to androgen deprivation. Taken together, our comprehensive study explores determinants of outcome and highlights the opportunities and challenges associated with the establishment of stable tumor organoid lines derived from PCa patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Associations With Definitive Outcomes and Clinical Benefit of Cancer Drugs at the Time of Marketing Approval and in the Postmarketing Period.

BACKGROUND: Most anticancer drugs are approved by regulatory agencies based on surrogate measures. This article explores the variables associated with overall survival (OS), quality of life (QoL), and substantial clinical benefit among anticancer drugs at the time of approval and in the postmarketing period. METHODS: Anticancer drugs approved by the FDA between January 2006 and December 2015 and with postmarketing follow-up until April 2019 were identified. We evaluated trial-level data supporting approval and any updated OS and/or QoL data. We applied the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the ASCO Value Framework (ASCO-VF) to initial and follow-up studies. RESULTS: We found that 58 drugs were approved for 96 indications based on 96 trials. At registration, approval was based on improved OS in 39 trials (41%) and improved QoL in 16 of 45 indications (36%). Postmarketing data showed an improvement in OS for 28 of 59 trials (47%) and in QoL for 22 of 48 indications (46%). At the time of approval, 25 of 94 (27%) and 26 of 80 scorable trials (33%) met substantial benefit thresholds using the ESMO-MCBS and ASCO-VF, respectively. In the postmarketing period, 37 of 69 (54%) and 35 of 65 (54%) trials met the substantial benefit thresholds. Drugs with companion diagnostics and immune checkpoint inhibitors were associated significantly with substantial clinical benefit. CONCLUSIONS: Compared with the time of approval, more anticancer drugs showed improved OS and QoL and met the ESMO-MCBS or ASCO-VF thresholds for substantial benefit over the course of postmarketing time. However, only approximately half of the trials met the threshold for substantial benefit. Companion diagnostic drugs and immunotherapy seemed to be associated with greater clinical benefit.

Reporting of Randomized Trials in Common Cancers in the Lay Media.

BACKGROUND: Limited data exist about the role of the lay media in the dissemination of results of randomized controlled trials (RCTs) in common cancers. METHODS: Completed phase III RCTs evaluating new drugs in common cancers between January 2005 and October 2016 were identified from ClinicalTrials.gov. Lay media reporting was identified by searching LexisNexis Academic. Scientific reporting was defined as presentation at an academic conference or publication in full. Associations between reporting in the lay media before scientific reporting and study design and sponsorship were evaluated using logistic regression. RESULTS: Of 180 RCTs identified, 52% were reported in the lay media and in 27%, lay media reporting occurred before scientific reporting with an increasing trend over time (p = 0.009). Reporting in the lay media before scientific reporting was associated with positive results (OR: 2.10, p = 0.04), targeted therapy compared to chemotherapy (OR: 4.75, p = 0.006), immunotherapy compared to chemotherapy (OR: 7.60, p = 0.02), and prostate cancer compared to breast cancer (OR: 3.25, p = 0.02). CONCLUSIONS: Over a quarter of all RCTs in common cancers are reported in the lay media before they are reported scientifically with an increasing proportion over time. Positive trials, studies in prostate cancer, and trials of immunotherapy are associated with early reporting in the lay media.

Neutrophils in cancer: prognostic role and therapeutic strategies.

Expression of high levels of immune cells including neutrophils has been associated with detrimental outcome in several solid tumors and new strategies to decrease their presence and activity are currently under clinical development. Here, we review some of the relevant literature of the role of neutrophils in different stages of the oncogenic process including tumor initiation, growth, proliferation or metastatic spreading and also focus on how neutrophil counts or the neutrophil-to-lymphocyte ratio may be used as a prognostic and predictive biomarker. Strategies to avoid the deleterious effects of neutrophils in cancer and to reduce their activity are discussed. Examples for such strategies include inhibition of CXCR1 and CXCR2 to decrease migration of neutrophils to tumoral areas or the inhibition of granulocyte colony stimulating factor to decrease the amount of neutrophils which has shown efficacy in preclinical models.

Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis.

BACKGROUND: Presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with gynecologic cancers, and examine the effect of clinico-pathologic factors on its prognostic value. METHODS: A systematic search of electronic databases was conducted to identify publications exploring the association of pre-treatment blood NLR with overall survival (OS) and event-free survival (EFS) among patients with ovarian, endometrial and cervical cancers. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p-value (P) were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to primary tumor type. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on the HR for OS and EFS. All statistical tests were two-sided. RESULTS: Twenty-six studies comprising 10,530 patients were included. Studies used different cut-offs to classify high NLR (range 0.89 to 5.03). The median cut-off for high NLR was 2.95 among twenty-six studies reporting a HR for OS, and 2.79 in seventeen studies reporting EFS outcomes. NLR greater than the cut-off was associated with worse OS (HR 1.65, 95% CI=1.44 to 1.89; P<0.001) and EFS (HR 1.57, 95% CI=1.35 to 1.82; P<0.001). This association was present in all tumor types. Most studies were comprised of patients with both early-stage and advanced disease. In cervical cancer, significant associations between NLR and OS were observed in studies of early- and mixed-stage patients and regression analysis showed a greater magnitude of effect in patients with locally advanced disease and in those who received both chemotherapy and radiation. CONCLUSIONS: High NLR is associated with an adverse OS and EFS in patients with gynecologic malignancies.

Prognostic role of telomere length in malignancies: A meta-analysis and meta-regression.

Telomere length (TL) has been associated with several health conditions including cancer. To quantify the effect of TL on outcomes in malignancies and explore the role of type of TL measurement we conducted a librarian-led systematic search of electronic databases identified publications exploring the prognostic role of TL on cancer outcomes. Overall survival (OS) was the primary outcome measure while other time-to-event endpoints were secondary outcomes. Data from studies reporting a hazard ratio (HR) with 95% confidence interval (CI) and/or p-value were pooled in a meta-analysis. HRs were weighted by generic inverse variance and computed by random effects modeling. All statistical tests were two-sided. Sixty-one studies comprising a total of 14,720 patients were included of which 41 (67%) reported OS outcomes. Overall, the pooled HR for OS was 0.88 (95%CI=0.69-1.11, p=0.28). Long (versus short) telomeres were associated with improved outcomes in chronic lymphatic leukemia (CLL) and urothelial cancer (HR=0.45, 95%CI=0.29-0.71 and HR=0.68, 95%CI=0.46-1.00, respectively), conversely worse OS was seen with hepatocellular carcinoma (HR=1.90, 95%CI=1.51-2.38). Pooled HRs (95% CI) for progression-free survival, relapse/disease-free survival, cancer-specific survival, and treatment-free survival were 0.56 (0.41-0.76), 0.76 (0.53-1.10), 0.72 (0.48-1.10), and 0.48 (0.39-0.60), respectively. There was substantial heterogeneity of tissues and methods used for TL measurement and no clear association between TL and outcome was identified in subgroups. In conclusion, there is inconsistent effect of TL on cancer outcomes possibly due to variable methods of measurement. Standardization of measurement and reporting of TL is warranted before the prognostic value of TL can be accurately assessed.

Under-reporting of harm in clinical trials.

Appropriate safety evaluations of anticancer drugs are crucial to assess their benefit-risk ratio. Substantial evidence shows that clinicians under-report harm in clinical trials, and at least three factors contribute to this problem: assessment of harm by clinicians might not represent the experience of patients; harm might be detected within trials, but is not reported appropriately by investigators or reporting is influenced by sponsors; and short-term follow-up might not detect long-term and potentially serious toxicities. Additionally, because of the selection of patients with good functional status in clinical trials, study results might not apply to patients treated in everyday clinical practice. New approaches for the conduct, oversight, and reporting of clinical trials should include patient-reported assessment of side-effects. Effective pharmacovigilance programmes and large-scale observational studies are needed to improve understanding of the tolerability of anticancer drugs in a real world setting.

Relevance of randomised controlled trials in oncology.

Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing.

Study of testosterone-guided androgen deprivation therapy in management of prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) with luteinizing hormone releasing hormone (LHRH) agonists is an effective initial therapy for men with advanced prostate cancer. LHRH agonists are usually administered indefinitely at a fixed interval. METHODS: We recruited men with advanced prostate cancer who had been on fixed-schedule injections of an LHRH agonist for ≥1 year and had castrate serum testosterone [<1.75 nmol/l (approx. 50 ng/ml)]. Testosterone levels were measured at 6-week intervals and ADT was withheld until testosterone levels were no longer in the castrate range and then reinstituted. Time to reinstitution of ADT was the primary outcome and was analyzed by the Kaplan-Meier method; Cox regression was used to identify factors predicting delay in reinstitution of treatment. Influence on quality-of-life (QoL) was evaluated by the Expanded Prostate Index Composite (EPIC). RESULTS: Forty-six evaluable men who had received LHRH agonist injections every 12 weeks were recruited. Median time to testosterone recovery (defined as testosterone outside the defined castrate level) after previous injection was >1 year. In univariable analysis, lower baseline testosterone [≤1 vs. >1 nmol/l (approx. 30 ng/dl)] and longer time on ADT (>5 vs. ≤5 years) predicted for prolonged time to testosterone recovery, but only lower baseline testosterone remained significant in multivariable analysis (Hazard Ratio = 5.2, P = 0.03). Overall EPIC scores remained stable but improvement from baseline was observed in the hormonal domain (P = 0.002). Median per-patient saving in cost was approximately USD 3,100 (1,050-6,200). CONCLUSIONS: Testosterone-guided ADT reduces exposure to LHRH agonists, with reduction in cost and improvement in some symptoms from ADT. Testosterone-guided ADT should be considered an alternative to fixed schedule treatment by physicians and policy makers.

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone.

BACKGROUND: Abiraterone acetate (AA), oral CYP17 inhibitor, is an active agent in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). METHODS: We (R.L.A and N.A) retrospectively evaluated outcome in 12 men who were re-treated with AA following prior treatment with AA at the Princess Margaret Cancer Centre. RESULTS: All men were heavily pre-treated for mCRPC with a median of four prior lines of therapy, one of which was AA (given either pre- or post-chemotherapy). Eleven out of 12 (92%) men stopped their first treatment course of AA due to progression and one stopped for financial reasons. Seven men had a PSA decrease ≥50% following their first AA treatment, of which three (46%) had a PSA decrease ≥50% to AA re-treatment. The responses to AA re-treatment were generally short-lived with a median biochemical progression-free survival of 2.3 months and median treatment duration of 3.2 months. No PSA responses to AA re-treatment were seen in five men who did not have an initial PSA response to AA. CONCLUSIONS: Our data suggest that AA re-challenge may have limited benefit in select men with mCRPC, and warrants further formal research.

Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, has been reported to be a poor prognostic indicator in prostate cancer. Here we explore the use of the NLR to establish a simple prognostic score for men with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel. METHODS: In the training cohort, the NLR and other known prognostic variables were evaluated among a cohort of chemotherapy-naïve patients treated with thrice-weekly docetaxel at the Princess Margaret Cancer Centre. Significant prognostic variables identified by univariable Cox regression were evaluated by the area under the receiver operating characteristic curves. Multivariable Cox regression was then used to derive a prognostic score where 1 risk point was assigned for each significant variable. The model was externally validated in a cohort of patients treated at the Royal Marsden. RESULTS: Three hundred fifty-seven patients were analyzed in the training cohort. Median age was 71 years, 12% had liver metastasis, and median overall survival (OS) was 14.7 months. Liver metastases, hemoglobin <12 g/dL, alkaline phosphatase >2.0× upper limit of normal (ULN), lactate dehydrogenase >1.2× ULN, and NLR >3 were associated with significantly worse OS in multivariable analysis. Four risk categories were subsequently established with 0, 1, 2, and 3-5 points. Two-year OS rates for these categories were 43%, 37%, 12%, and 3%, respectively. Area under the curve for the training cohort was 0.78 (95% CI, 0.72-0.84) compared with 0.66 (95% CI, 0.58-0.74) for the 215 patients in the validation cohort. CONCLUSIONS: This simple risk score provides good prognostic and discriminatory accuracy for men with mCRPC.

Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis.

Women with multifocal or multicentric breast tumors (multifocality henceforth) have been reported to have greater probability of nodal metastasis and relapse and worse survival than women with unifocal tumors. However, these associations have been inconsistent and multifocality is not taken into account by staging guidelines and prognostic models. A systematic review of electronic databases identified publications exploring the association between multifocality and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and loco-regional relapse (LRR). The hazard ratios (HRs) for OS and DFS for multifocal compared to unifocal tumors were extracted from multivariable analyses and included in a meta-analysis. For studies not reporting multivariable analyses, odds ratios (OR) were estimated from Kaplan-Meier curves for all endpoints at 5 and 10 years. Twenty-two studies comprising 67,557 women were included. Multifocality was reported in 9.5 % of patients. Classical prognostic factors were well balanced between unifocal and multifocal populations. In multivariable analyses, multifocality was associated with significantly worse OS (HR 1.65; P = 0.02), and a non-significant association with worse DFS (HR 1.96; P = 0.07). In univariable analyses, multifocality was associated with worse OS, DFS, DSS, and LRR at 5 years (OR 1.39, P = 0.02; OR 1.52, P = 0.02; OR 1.56, P = 0.03; and OR 3.23, P = 0.02, respectively). Similar estimates were observed at 10 years, but statistical significance was only reached for DSS and LRR. Mutifocality appears to be associated with a worse prognosis, however, substantial inter-study heterogeneity limits the precise determination of increased risk. Further validation of the independent prognostic impact of multifocality is warranted.

Factors impacting survival following second surgery in patients with glioblastoma in the temozolomide treatment era, incorporating neutrophil/lymphocyte ratio and time to first progression.

Patients with progressive glioblastoma (GBM) have a poor prognosis. Neutrophil/lymphocyte ratio (NLR), a host inflammatory marker, is prognostic in several solid tumors. The prognostic impact of either NLR, or time from first surgery for GBM to first progression (TTP), in patients undergoing second surgery, has not been assessed. Patients undergoing second surgery for GBM were retrospectively reviewed. Primary outcome was overall survival (OS) and Cox proportional hazard models were used to assess the prognostic value of baseline characteristics including TTP and NLR. Univariable and multivariable analysis (MVA) of OS from second surgery were performed using accelerated failure time Weibull model. Of 584 patients with GBM, 107 (18 %) underwent second surgery between 01/04 and 12/11. Patients who underwent second surgery had longer OS versus those having primary surgery alone; 20.9 versus 9.9 months (P < 0.001). Median OS from second surgery in patients with NLR ≤ 4 versus NLR > 4 was 9.7 versus 5.9 months (log rank P = 0.02). The NLR retained its prognostic significance for survival on MVA (time ratio [TR] 1.65, 95 % confidence interval [CI] 1.15-2.35, P < 0.01). No chemotherapy post second surgery (TR 0.23, 95 % CI 0.16-0.33, P < 0.001) portended worse survival. In patients undergoing second surgery, when TTP was ≤ 12 months, 12-24 months, or >24 months, median OS from second surgery was 7.2, 7.0 and 6.3 months, respectively (P = 0.6). A NLR > 4 prior to second surgery is a poor prognostic factor in GBM and later progression is associated with longer survival in patients but not in longer survival after second surgery.

Cross-sectional study of self-reported physical activity, eating habits and use of complementary medicine in breast cancer survivors.

BACKGROUND: Besides conventional adjuvant therapies, many breast cancer survivors engage in various activities like exercise, diet and complementary and alternative medicine (CAM) in order to improve their prognosis. Little is known about specific interests and willingness to participate in institutional programs (e.g. exercise classes). METHODS: We conducted a cross-sectional study in patients with early breast cancer assessing current physical activity (PA, e.g. 30 minutes brisk walking), attention to eating habits ("diet"), use of CAM, and interest in learning more about these fields. Patients indicating interest in PA counselling received a voucher for a free instruction by a certified physiotherapist. Data were analysed for factors predictive for engagement in the three fields using a stepwise multivariate logistic approach. RESULTS: Of 342 consecutive patients, 232 (69%) reported to be physically active more than once per week, 299 (87%) paying special attention to nutrition (in most cases fruits, "balanced diet", low fat), and 159 (46%) use of CAM (vitamins, special teas, homeopathy, herbal medicine, mistletoe). Factors predictive for PA were use of CAM, higher age, and fewer worries about the future. Swiss nationality at birth, physical activity and higher education were predictive for diet; whereas physical activity, higher education and lower age were predictive for use of CAM. No associations between any of the above variables and breast cancer characteristics were found. Around half of the patients reported interest in receiving more information and willingness to attend special counselling. Of 166 vouchers, only 7 (4%) were eventually utilized. CONCLUSIONS: A high proportion of breast cancer survivors report PA, following a specific diet and use of CAM. There were no disease related factors associated with such pursuits, but an association between patient related factors and these fields was observed suggesting general health awareness in some patients. Around half of the patients were interested in more information and indicated willingness to participate in institutional programs. Impact on disease specific and general health including health economic aspects warrants further research.

Benefit and harms of new anti-cancer drugs.

Phase III randomized controlled trials (RCTs) assess clinically important differences in endpoints that reflect benefit to and harm of patients. Defining benefit of cancer drugs can be difficult. Overall survival and quality of life are the most relevant primary endpoints, but difficulty in measuring these mean that other endpoints are often used, although their surrogacy or clinical relevance has not always been established. In general, advances in drug development have led to numerous new drugs to enter the market. Pivotal RCT of several new drugs have shown that benefit appeared greater for targeted anticancer agents than for chemotherapeutic agents. This effect seems particularly evident with targeted agents evaluated in biomarker-driven studies. Unfortunately, new therapies have also shown an increase in toxicity. Such toxicity is not always evident in the initial reports of RCTs. This may be a result of a statistical inability to detect differences between arms of RCTs, or occasionally due to biased reporting. There are several examples where reports of new toxicities could only be found in drug labels. In some cases, the small improvement in survival has come at a cost of substantial excess toxicity, leading some to consider such therapy as having equipoise.

The trajectory of sarcopenia following diagnosis of prostate cancer: A systematic review and meta-analysis.

INTRODUCTION: Sarcopenia is a common skeletal muscle disorder in older people. Here we explore the prevalence of sarcopenia and its impact on men with prostate cancer. MATERIALS AND METHODS: We searched PubMed, Embase, and Web of Science databases for relevant studies with an explicit definition of sarcopenia in men with prostate cancer which were published between years 2000 and 2022. Prevalence of sarcopenia and its association with time to biochemical recurrence (BCR), progression-free survival (PFS), non-cancer mortality, overall survival (OS), and treatment-related complications in men with prostate cancer were explored. The summary prevalence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 24 studies comprising 3,616 patients with early and advanced prostate cancer were included. The prevalence of sarcopenia and sarcopenic obesity was 43.8% (95% CI 19.2%-68.5%) and 24.0% (95% CI 5.0%-43.1%), respectively. Sarcopenia was not associated with a shorter time to BCR (HR 0.89, 95% CI 0.64-1.23, p = 0.48), a shorter PFS (HR 1.20, 95% CI 0.73-1.97, p = 0.48), or a shorter OS (HR 1.29, 95% CI 0.90-1.85, p = 0.16). In contrast, sarcopenia was significantly associated with a higher non-cancer mortality (HR 1.85, 95% CI 1.23-2.80, p = 0.003). In four out of five studies eligible for assessment, sarcopenia was not associated with an increased risk of treatment-related complications. DISCUSSION: Sarcopenia increases the risk of death from other causes in men with prostate cancer. Patients with prostate cancer should be assessed and managed for sarcopenia in everyday clinical practice.

Diagnosis and Treatment of Patients Utilizing Complementary Medicine at a Tertiary Referral Hospital in Eastern Switzerland.

BACKGROUND: In 2012, the Cantonal Hospital of St. Gallen, a tertiary referral hospital in Eastern Switzerland, opened its Center for Integrative Medicine (ZIM). This study aims to characterize disease and treatment characteristics of adult patients treated at the ZIM. PATIENTS AND METHODS: For all new patients, physicians at the ZIM completed questionnaires on patients' diagnoses and treatments. Descriptive statistics for categorical variables were reported as percentages. Univariable logistic regression analysis was used to assess the data. The analysis was performed with the statistical software package SPSS (IBM). RESULTS: From 2015 to 2020, 4,592 new patients were seen at the ZIM. The most common diagnosis in the supergroups was cancer (48%), followed by pain diagnoses (33%). Chronic pain as a subgroup was represented the most in patients (29%). Anthroposophical medication was the most commonly prescribed therapy, in 74% of patients with cancer and 73% with pain diagnosis. The latter was associated with the prescription of eurythmy therapy (OR: 3.80, p < 0.001), traditional Chinese medicine (OR: 3.34, p < 0.001), or art therapy (OR: 5.15, p < 0.001), whereas mistletoe therapy was the preferred treatment option (OR: 59.0, p < 0.001) for a cancer diagnosis. CONCLUSION AND OUTLOOK: The results will help adapt CM services to patients' needs and provide a good basis for the planning of future services in CM in major hospitals. Further research should be conducted focusing on specific health outcomes.

Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition.

OBJECTIVES: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). METHODS: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. RESULTS: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. CONCLUSIONS: Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.

Additional Primary Tumors Detected Incidentally on FDG PET/CT at Staging in Patients with First Diagnosis of NSCLC: Frequency, Impact on Patient Management and Survival.

We aimed to assess the frequency of additional primary malignancies detected incidentally on [18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) at staging in NSCLC patients. Moreover, their impact on patient management and survival was assessed. Consecutive NSCLC patients with available staging FDG-PET/CT between 2020 and 2021 were retrospectively enrolled. We reported whether further investigations of suspicious findings presumably not related to NSCLC were recommended and performed after FDG-PET/CT. Any additional imaging, surgery or multimodal management was considered as an impact on patient management. Patient survival was defined using overall survival OS and progression-free survival PFS. A total of 125 NSCLC patients were included, while 26 findings in 26 different patients were suspicious for an additional malignancy on FDG-PET/CT at staging. The most frequent anatomical site was the colon. A total of 54.2% of all additional suspicious lesions turned out to be malignant. Almost every malignant finding had an impact on patient management. No significant differences were found between NSCLC patients with suspicious findings versus no suspicious findings with regards to their survival. FDG-PET/CT performed for staging might be a valuable tool to identify additional primary tumors in NSCLC patients. Identification of additional primary tumors might have substantial implications for patient management. An early detection together with interdisciplinary patient management could prevent a worsening of survival compared to patients with NSCLC only.