Challenges in the management of operable triple-negative breast cancer in a survivor of the B-cell acute lymphoblastic leukemia: a case report.

Background: Operable triple-negative breast cancer (TNBC) is an unfavorable subtype of breast cancer, which usually requires an aggressive perioperative systemic treatment. When TNBC presents as a second primary cancer after cured acute leukemia, its management might be challenging. Case presentation: We present a case report of a young postmenopausal woman with an operable TNBC who had a history of the B-cell acute lymphoblastic leukemia (B-ALL) and graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). A history of previous treatment with anthracyclines and radiotherapy and GVHD limited the use of doxorubicin for treatment of her TNBC. Due to the history of GVHD, perioperative treatment with pembrolizumab was omitted. Genetic testing was challenging due to the possible contamination of her tissues with the donor's cells after allo-SCT. In samples of our patient's buccal swab, peripheral blood, and tumor tissue, a pathogenic variant in the partner and localizer of BRCA2 (PALB2) gene was found. With neoadjuvant chemotherapy which included carboplatin, a pathologic complete response was achieved. Although our patient has a low risk for recurrence of TNBC, her risk for the development of new primary cancers remains substantial. Conclusion: This case highlights challenges in the systemic treatment, genetic testing, and follow-up of patients with operable TNBC and other solid cancers who have a history of acute leukemia.

Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management.

BACKGROUND: Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. RESULTS: Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. CONCLUSIONS: Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.

Association of androgen receptor and tumour-infiltrating lymphocytes with bone recurrence in triple-negative breast cancer.

Background: As compared to endocrine responsive breast cancer bone is less frequent site of distant recurrence in triple-negative breast cancer (TNBC). A biomarker which predicts bone recurrence would allow a more personalized treatment approach with adjuvant bisphosphonates in TNBC. Here we hypothesised that tumour expression of androgen receptor (AR) is associated with bone recurrence in TNBC. Materials and methods: Patients with operable TNBC who were treated at the Institute of Oncology Ljubljana between 2005 and 2015 and developed distant recurrence were included into our study. Nuclear expression of AR in the tissue of primary tumours was determined immunohistochemically by using the Androgen Receptor (SP107) Rabbit Monoclonal Antibody. We applied a logistic regression model to test the association between expression of AR and development of bone metastases. The model was adjusted for selected known prognostic factors and possible confounders in TNBC, including the level of the stromal tumour-infiltrating lymphocytes (sTILs). Results: At recurrence 45 (45 %) out of 100 patients presented with bone metastases. Additionally, seven (7 %) developed bone metastases metachronously. AR was expressed in primary tumours of 35 (35 %) women and 19 (54.3 %) developed bone recurrence. In 25 (25 %) patients sTILs were absent. Neither the proportion of AR positive cancer cells (OR = 1.00; 95 % CI 0.96-1.03; p = 1.00) nor the intensity of AR positive reaction (OR = 0.71; 95 % CI 0.02-21.4; p = 1.00) were significantly associated with bone recurrence. However, women with at least mild level of the sTILs were at significantly lower risk for bone recurrence as compared to those without any sTILs (OR = 0.01; 95 % CI < 0.01-0.08; p = 0.01). Conclusions: Expression of AR is not significantly associated with the development of bone metastases in TNBC. However, patients with absent sTILs in their primary tumours are highly susceptible for recurrence in the bone and might particularly benefit from adjuvant bisphosphonates.

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.

Association between PIK3CA activating mutations and outcomes in early-stage invasive lobular breast carcinoma treated with adjuvant systemic therapy.

BACKGROUND: The aim of the study was to evaluate the independent prognostic role of PIK3CA activating mutations and an association between PIK3CA activating mutations and efficacy of adjuvant endocrine therapy (ET) in patients with operable invasive lobular carcinoma (ILC). PATIENTS AND METHODS: A single institution study of patients with early-stage ILC treated between 2003 and 2008 was performed. Clinicopathological parameters, systemic therapy exposure and outcomes (distant metastasis-free survival [DMFS] and overall survival [OS]) were collected based on presence or absence of PIK3CA activating mutation in the primary tumor determined using a quantitative polymerase chain reaction (PCR)-based assay. An association between PIK3CA mutation status and prognosis in all patient cohort was analyzed by Kaplan-Meier survival analysis, whereas an association between PIK3CA mutation and ET was analyzed in estrogen receptors (ER) and/or progesterone receptors (PR)-positive group of our patients by the Cox proportional hazards model. RESULTS: Median age at diagnosis of all patients was 62.8 years and median follow-up time was 10.8 years. Among 365 patients, PIK3CA activating mutations were identified in 45%. PIK3CA activating mutations were not associated with differential DMFS and OS (p = 0.36 and p = 0.42, respectively). In patients with PIK3CA mutation each year of tamoxifen (TAM) or aromatase inhibitor (AI) decreased the risk of death by 27% and 21% in comparison to no ET, respectively. The type and duration of ET did not have significant impact on DMFS, however longer duration of ET had a favourable impact on OS. CONCLUSIONS: PIK3CA activating mutations are not associated with an impact on DMFS and OS in early-stage ILC. Patients with PIK3CA mutation had a statistically significantly decreased risk of death irrespective of whether they received TAM or an AI.

Prognostic Impact of Nutritional Status on Overall Survival and Health-Related Quality of Life in Men with Advanced Prostate Cancer.

PURPOSE: Prognostic role of nutritional status (NS) in patients with metastatic castrate-resistant prostate cancer (mCRPC) is unknown. We hypothesized that patients' NS at the presentation of mCRPC is prognostic for health-related quality of life (HRQoL) and overall survival (OS). METHODS: We conducted a prospective observational study in mCRPC patients. At enrollment, we allocated each patient into one of four NS categories: (i) well-nourished (WN), (ii) nutritional risk without sarcopenia/cachexia (NR), (iii) sarcopenia, or (iv) cachexia. We sought the prognostic role of the NS for OS and HRQoL by regression models. RESULTS: 141 patients were included into our study. When compared to WN patients, those with NR and cachexia had a higher chance of worse HRQoL (OR 3.45; 95% CI [1.28 to 9.09], and OR 4.17; 95% CI [1.28 to 12.5], respectively), as well as shorter OS (HR 2.04; 95% CI [1.19 to 3.39] and HR 2.9; 95% CI [1.56 to 5.41], respectively). However, when accounting for possible confounding factors, we could not prove the significant importance of NS for chosen outcomes. CONCLUSIONS: Suboptimal NS might be an unfavorable prognostic factor for HRQoL and OS. Further interventional studies focusing on therapy or prevention are warranted.

Perspectives for Cancer Care and Research in Central and Eastern Europe.

BACKGROUND: Discrepancies between the outcomes of cancer patients between Western European and Central and Eastern European (CEE) countries have often been observed. Despite the enormous economic and civilizational progress made in these countries after the abolishment of the communist regime, structural problems persist. SUMMARY: The present article reviews the domains of medical oncology education, human resources in oncology, cancer care, and clinical research in CEE in order to comprehensively assess the current situation and needs, describe important initiatives, and also propose ways to improving cancer outcomes in the region. Activities are under way to address these issues in national action plans to divert funding into oncology-related education, research, the purchase of equipment, and the attainment of modern hospital organization and structures. KEY MESSAGE: Over the past more than 30 years, CEE countries have made enormous economic and societal progress. Nevertheless, challenges especially in the health care sector persist.

Clinical benefit of cancer drugs approved in Switzerland 2010-2019.

BACKGROUND: It is unknown to what extent cancer drugs approved in Switzerland by the Swissmedic fulfil criteria of clinical benefit according to the European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS), the American Society of Clinical Oncology Value Framework version 2 (ASCO-VF) and the Swiss OLUtool v2 (OLUtool). PATIENTS AND METHODS: An electronic search identified studies that led to marketing authorisations in Switzerland 2010-2019. Studies were evaluated according to ESMO-MCBS, ASCO-VF and OLUtool. Substantial benefit for ESMO-MCBS, was defined as a grade A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. For ASCO-VF and OLUtool clinical benefit was defined as score ≥45 and A or B, respectively. Concordance between the frameworks was calculated with Cohen's Kappa (κ). Factors associated with clinical benefit were evaluated by logistic regression. RESULTS: In the study period, 48 drugs were approved for 92 evaluable indications, based on 100 studies. Ratings for ESMO-MCBS, ASCO-VF and OLUtool could be performed for 100, 86, and 97 studies, respectively. Overall, 39 (39%), 44 (51%), 45 (46%) of the studies showed substantial clinical benefit according to ESMO-MCBS v1.1, ASCO-VF, OLUtool criteria, respectively. There was fair concordance between ESMO-MCBS and ASCO-VF in the palliative setting (κ = 0.31, P = 0.004) and moderate concordance between ESMO-MCBS and OLUtool (κ = 0.41, P<0.001). There was no significant concordance between ASCO-VF and OLUtool (κ = 0.18, P = 0.12). Factors associated with substantial clinical benefit in multivariable analysis were HRQoL benefit reported as secondary outcome for ESMO-MCBS and the ASCO-VF and blinded studies for OLUtool. CONCLUSIONS: At the time of approval, only around half of the trials supporting marketing authorisation of recently approved cancer drugs in Switzerland meet the criteria for substantial clinical benefit when evaluated with ESMO-MCBS, ASCO-VF or OLUtool. There was at best only moderate concordance between the grading systems.

Nutritional Status and Health-Related Quality of Life in Men with Advanced Castrate-Resistant Prostate Cancer.

Background Despite professional recommendations malnutrition is not adequately addressed in cancer patients. Here, we explored whether nutritional status (NS) is associated with HRQoL in men with metastatic castrate-resistant prostate cancer (mCRPC). Methods: Men with mCRPC enrolled into this prospective observational study were allocated to one of the four NS categories based on clinical, laboratory, and patient self-reported criteria: well-nourished (WN), nutritional risk without criteria for cachexia/sarcopenia (NR), sarcopenia, and cachexia. The HRQoL was evaluated by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Association between NS and self-reported HRQoL was sought by the linear regression model, which was adjusted for known prognostic variables and body mass index. Results: Over the period of two years, 141 patients were enrolled. Their median age was 74.1 years (IQR 68.6-79.4 years) and majority of them were minimally symptomatic. Fifty-nine patients (41.8%) were WN, followed by 24 (17%), 42 (29.8%), and 16 (11.4%) patients with NR, sarcopenia, and cachexia, respectively. As compared to WN patients, all three other NS categories were significant negative predictors of HRQoL (P < 0.04). Conclusions: Abnormal NS is highly prevalent in men with mCRPC and is negatively associated with their HRQoL, which supports the recommendation for management of malnutrition in these patients.

Efficacy, safety and tolerability of drugs studied in phase 3 randomized controlled trials in solid tumors over the last decade.

Data suggest that for newly approved cancer drugs safety and tolerability are worse than in control arms of registration trials. Less is known about the balance between efficacy and toxicity of drugs studied in unselected phase 3 randomized controlled trials (RCTs) including those not resulting in regulatory approval. We searched Clinicaltrials.gov to identify phase 3 RCTs in patients with advanced breast, colorectal, lung, or prostate cancer completed between January 2005 and October 2016. We extracted efficacy and safety data from publications. For efficacy hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were extracted. For safety, we computed odds ratios (ORs) and 95% confidence intervals (CIs) for toxic death, treatment discontinuation without progression and commonly reported grade 3/4 adverse events (AEs). Data were then pooled in a meta-analysis. Of 377 RCTs identified initially, 143 RCTs comprising 88,603 patients were included in the analysis. Of these, 79 (57%) trials met their primary endpoint. Compared to control groups, both PFS (HR 0.80; 95% CI 0.78-0.82) and OS (HR 0.87; 95% CI 0.85-0.89) were improved with experimental drugs. Toxic death (OR 1.14; 95% CI 1.03-1.27), treatment discontinuation without progression (OR 1.64; 95% CI 1.56-1.71) and grade 3/4 AEs were also more common with experimental drugs compared to respective control group therapy. Just over half of phase 3 RCTs in common solid tumors met their primary endpoint and in nearly half, experimental therapy had worse safety compared to control arms.

Updating Reports of Phase 3 Clinical Trials for Cancer.

IMPORTANCE: Phase 3 randomized clinical trials (RCTs) are usually reported after a predetermined number of events (death or disease progression) have occurred, when survival curves remain poorly defined. Updated reports are important in providing mature data. OBJECTIVES: To evaluate the proportion of phase 3 RCTs for cancer that are updated and the factors that are associated with updating them and, for updated trials, to compare initial and updated results. DESIGN, SETTING, AND PARTICIPANTS: This study identified reports of 2-group RCTs with a sample size of at least 100, published in 6 major journals between 1990 and 2010, that evaluated drug treatments for breast, lung, or prostate cancer. PubMed and abstracts of large cancer conferences were searched to identify updated (or earlier) reports of the same trials published up to 2019. Logistic regression was used to identify factors associated with the provision of updated reports. The hazard ratios defining the relative treatment effects for the primary and secondary end points between the initial and updated reports were compared. MAIN OUTCOMES AND MEASURES: Proportion of RCTs whose results are updated, factors associated with updating, and change in hazard ratio for the primary end point between initial and updated reports. RESULTS: A total of 207 RCTs met the inclusion criteria, and 41 (20%) were found to have updated reports. The factors significantly associated with an update included positive trial results (odds ratio [OR], 8.7 [95% CI, 3.3-23.3]), larger trial size (OR, 1.0006 [95% CI, 1.0000-1.0012]), evaluation of hormonal agents (OR, 5.8 [95% CI, 1.6-21.8]) or targeted agents (OR, 4.3 [95% CI, 1.3-14.6]) compared with chemotherapy, and evaluation of adjuvant therapy rather than therapy for advanced disease (OR, 8.0 [95% CI, 2.9-21.9]). For 31 trials for which initial and updated hazard ratios for the primary end point were available, the median hazard ratio increased from 0.66 (95% CI, 0.22-1.20) to 0.74 (95% CI, 0.32-1.19) (P < .001), indicating a decreased level of effectiveness. CONCLUSIONS AND RELEVANCE: Only 20% of reports of phase 3 clinical trials for breast, lung, and prostate cancer were updated. Original reports of such trials are based on relatively few events, and their results are immature; more mature data indicate a decreased level of effect in updated trials. Updated reporting to provide mature, long-term results of clinical trials should be mandated.

Training of oncologists: results of a global survey.

While several studies have highlighted the global shortages of oncologists and their workload, few have studied the characteristics of current oncology training. In this study, an online survey was distributed through a snowball method for cancer care providing physicians in 57 countries. Countries were classified into low- or lower-middle-income countries (LMICs), upper-middle-income countries (UMICs) and high-income countries (HICs) based on World Bank criteria. A total of 273 physicians who were trained in 57 different countries responded to the survey: 33% (90/273), 32% (87/273) and 35% (96/273) in LMICs, UMICs and HICs, respectively. About 60% of respondents were practising physicians and 40% were in training. The proportion of responding trainees was higher in LMICs (51%; 45/89) and UMICs (42%; 37/84), than HICs (19%; 28/96; p = 0.013). A higher proportion of respondents from LMICs (37%; 27/73) self-fund their core oncology training compared to UMICs (13%; 10/77) and HICs (11%; 10/89; p < 0.001). Respondents from HICs were more likely to complete an accepted abstract, poster and publication from their research activities compared to respondents from UMICs and LMICs. Respondents identified several barriers to effective training, including skewed service to education ratio and burnout. With regard to preparedness for practice, mean scores on a 5-point Likert scale were low for professional tasks like supervision and mentoring of trainees, leadership and effective management of an oncology practice and understanding of healthcare systems irrespective of country grouping. In conclusion, the investment in training by the public sector is vital to decreasing the prevalence of self-funding in LMICs. Gaps in research training and enhancement of competencies in research dissemination in LMICs require attention. The instruction on cancer care systems and leadership needs to be incorporated in training curricula in all countries.

Associations between safety, tolerability, and toxicity and the reporting of health-related quality of life in phase III randomized trials in common solid tumors.

BACKGROUND: Anti-cancer drugs are approved typically on the basis of efficacy and safety as evaluated in phase III randomized trials (RCTs). Health-related quality of life (HRQoL) is a direct measure of patient benefit, but is under-reported. Here we explore associations with reporting of HRQoL data in phase III RCTs in common solid tumors. METHODS: We searched ClinicalTrials.gov to identify phase III RCTs evaluating new drugs in adults with advanced cancers that completed accrual between January 2005 and October 2016. Data on HRQoL, safety, and tolerability comprising treatment-related death, treatment discontinuation and commonly reported grade 3 or 4 adverse events (AEs) were extracted. Associations between these measures and reporting of HRQoL data were explored using logistic regression. RESULTS: Of 377 phase III RCTs identified initially, 143 studies were analysed and comprised 55% positive trials and 90% industry sponsored trials. HRQoL was listed as an endpoint in 59% trials; and of these, only 65% reported HRQoL data. There were higher odds of reporting HRQoL data for positive trials (OR 2.05, P = .04) and trials published in journals with higher impact factor (OR 1.35, P = .01). Reporting of HRQoL was not associated with treatment-related death (OR 1.25, P = .40) or treatment discontinuation (OR 1.12, P = .61), but was positively associated with dyspnea and dermatological adverse events. CONCLUSIONS: HRQoL is reported in only two-thirds of RCTs that describe collecting such data. Reporting of HRQoL is associated with positive trial outcome and higher journal impact factor, but not associated with overall safety and tolerability of anti-cancer drugs.

Oncologist Burnout Syndrome in Eastern Europe: Results of the Multinational Survey.

PURPOSE: Burnout is defined as a three-dimensional syndrome-emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA)-caused by chronic occupational stress. The aim of the current study was to investigate the prevalence of burnout among oncologists in Eastern Europe and to identify the contributing factors. METHODS: The study was conducted as an online survey between October 2017 and March 2018. Oncologists (including medical, radiation, clinical, and surgical oncologists) from 19 countries were invited to participate. The survey consisted of 30 questions, including the standardized burnout instrument, Maslach Burnout Inventory, and eight demographic questions. Burnout risk was scored according to the scoring manual for health care workers. RESULTS: The study included 637 oncologists. Overall, 28% were at low or intermediate risk and 72% were at high risk for burnout. Forty-four percent of participants were at high risk for EE, 28.7% for DP, and 47.3% for PA. EE risk was associated with female sex. DP risk was highest among clinical and radiation oncologists, whereas PA risk was positively correlated with years of service, percentage of cancer deaths, and availability of the number of oncologists. In multivariate logistic regression analysis, burnout was significantly associated with standardized cancer mortality and fewer years of practice. CONCLUSION: Burnout among oncologists in Eastern Europe is high, and younger oncologists are the most vulnerable group. Preventive measures should be taken to address this issue, which negatively affects optimal care delivery and poses a threat to oncologists' health and well-being.

Adjuvant Radiation Therapy After Radical Nephrectomy in Patients with Localized Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

CONTEXT: Adjuvant radiation therapy has been recommended for patients at higher risk of relapse from renal cell carcinoma (RCC) to improve disease-free survival (DFS) and overall survival (OS) after radical nephrectomy. OBJECTIVE: To quantify the benefit of adjuvant radiation therapy. EVIDENCE ACQUISITION: A systematic review of electronic databases identified publications exploring the association between adjuvant radiation therapy and locoregional recurrence (LRR), DFS, and OS among patients after radical nephrectomy for early-stage RCC. Hazard ratios for DFS were weighted and pooled using the generic inverse variance and random effects model. Odds ratios for LRR, DFS, and OS at 5yr were weighted and pooled in a meta-analysis using Mantel-Haenszel random-effects modeling. EVIDENCE SYNTHESIS: Twelve studies comprising 1624 patients were included in the analysis. Ten studies were retrospective and two were randomized controlled trials. Adjuvant radiation therapy was delivered to 37% of patients. The median follow-up was 49mo. Adjuvant radiation therapy was not associated with better DFS or OS at 5yr, but was associated with less LRR. CONCLUSIONS: With the caveat that confounding by indication may result from pooling data from predominantly nonrandomized studies, adjuvant radiation after radical nephrectomy was not associated with improved DFS or OS but was associated with less LRR. PATIENT SUMMARY: Radiation therapy after resection of renal cell carcinoma with a high risk of relapse may reduce the risk of local recurrence but not the risk of disease recurrence or death after 5yr.

Cancer care workforce in Africa: perspectives from a global survey.

BACKGROUND: While the burden of cancer in Africa is rapidly rising, there is a lack of investment in healthcare professionals to deliver care. Here we report the results of a survey of systemic therapy workload of oncologists in Africa in comparison to oncologists in other countries. METHODS: An online survey was distributed through a snowball method via national oncology societies to chemotherapy-prescribing physicians in 65 countries. The survey was distributed within Africa through a network of physicians associated with the African Organisation for Research and Training in Cancer (AORTIC). Workload was measured as the annual number of new cancer patient consults seen per oncologist. Job satisfaction was ranked on a 10-point Likert scale; scores of 9-10 were considered to represent high job satisfaction. RESULTS: Thirty-six oncologists from 18 countries in Africa and 1079 oncologists from 47 other countries completed the survey. Compared to oncologists from other countries, African oncologists were older (median age 51 vs 44 years, p = 0.007), more likely to prescribe chemotherapy and radiation [61% (22/36) vs 10% (108/1079), p < 0.001], less likely to have completed training in their home country [50% (18/36) vs 91% (979/1079), p < 0.001], and more likely to work in the private sector [47% (17/36) vs 34% (364/1079), p = 0.037]. The median number of annual consults per oncologist was 325 in Africa compared to175 in other countries. The proportion of oncologists seeing > 500 consults/year was 31% (11/36) in Africa compared to 12% (129/1079) in other countries (p = 0.001). African oncologists were more likely than global colleagues to see all cancer sites [72% (26/26) vs 24% (261/1079), p < 0.001]. Oncologists in Africa were less likely than other oncologists to have high job satisfaction [17% (6/36) vs 30% (314/1079), p = 0.013]. CONCLUSION: African oncologists within the AORTIC network have a substantially higher clinical workload and lower job satisfaction than oncologists elsewhere in the world. There is an urgent need for governments and health systems to improve the oncologist-to-patient ratio and develop new models of capacity building, retention and skills enhancement to strengthen the wide variety of cancer care systems across continental Africa.

Medical oncology job satisfaction: Results of a global survey.

BACKGROUND: While physician burnout is increasingly recognized, little is known about medical oncologist job satisfaction, and the factors associated with low satisfaction. Here, we report the results of an international survey of medical oncologists. METHODS: An online survey was distributed using a modified snowball methodology via national oncology societies to chemotherapy-prescribing physicians in 65 countries. Oncologist job satisfaction was assessed by asking, "On a scale of 1-10, how would you rate your satisfaction as an oncologist? 1 = unsatisfying, 10 = satisfying." Low, moderate and high job satisfaction was defined as scores of 1-6, 7-8, and 9-10, respectively. RESULTS: 1,115 physicians from 42 countries completed the survey. Overall job satisfaction rates were 20% (222/1,115), 51% (573/1,115), and 29% (320/1,115) for low-, moderate-, and high-satisfaction, respectively. Respondents with low job satisfaction were younger (P = 0.001) and had fewer years in clinical practice (P = 0.013) compared to those with high satisfaction. Increasing hours worked by per week (p = 0.042), decreasing annual weeks of paid vacation (P = 0.007), being on-call every night (P = 0.016), higher clinic volumes (P = 0.004) and lack of access to on-site radiotherapy (P = 0.049), palliative care (P = 0.005), and chemotherapy pharmacists (P = 0.033) were associated with low-job satisfaction. Respondents with low-job satisfaction were less likely to discuss prognosis with their patients compared to those with moderate or high job satisfaction (median 45% of patients v 65% v 75%, P < 0.001). CONCLUSIONS: Globally, 1 in 5 medical oncologists report low job satisfaction. The main correlates of job satisfaction are related to system-level pressures resulting in less time for quality patient care and personal resilience. Improving oncologist job satisfaction will require new approaches to models of care delivery.

Postmarketing Safety-Related Modifications of Drugs Approved by the US Food and Drug Administration Between 1999 and 2014 Without Randomized Controlled Trials.

OBJECTIVE: To investigate whether US Food and Drug Administration approval of new drugs without randomization or an active drug comparator is associated with more postmarketing safety-related label modifications. METHODS: We searched Drugs@FDA for new drugs approved from January 1, 1999, through December 31, 2014. Drugs approved without supporting randomized controlled trials (RCTs) were matched to between 1 and 2 controls from similar therapeutic categories approved with supporting RCTs within 3 years of the reference drug. Study characteristics, regulatory pathways, and label modifications up to December 2017 were collected from drug labels. Differences in postmarketing safety modifications between cases and controls were assessed using conditional logistic regression. RESULTS: The study cohort included 52 drugs approved without supporting RCTs and 91 matched controls. Drug approvals not supported by RCTs were associated with lower sample size (odds ratio [OR] per 100 patients, 0.77; 95% CI, 0.68-0.87) and were more likely to receive orphan drug designation (OR, 5.10; 95% CI, 2.23-11.69), fast-track designation (OR, 4.80; 95% CI, 2.25-10.23), and accelerated approval (OR, 7.00; 95% CI, 3.14-15.60). Drugs approved without supporting RCTs were associated with more modifications in black box warnings (28.8% vs 13.2%; OR, 2.67; 95% CI, 1.13-6.27), warnings and precautions (73.1% vs 52.7%; OR, 2.43; 95% CI, 1.16-5.09), and common adverse reactions (48.1% vs 23.1%; OR, 3.09; 95% CI, 1.49-6.41). CONCLUSION: Food and Drug Administration approval of new drugs without supporting RCTs is associated with more postmarketing safety-related label modifications than drugs approved with supporting RCTs. Robust postmarketing studies are required for drugs approved without supporting RCTs. Health care professionals should be vigilant for unrecognized adverse effects when prescribing these drugs.

Meta-Research on Oncology Trials: A Toolkit for Researchers with Limited Resources.

"Meta-research" is a discipline that investigates research practices. Meta-research on clinical trials is an attempt to summarize descriptive and methodological features of published or ongoing clinical trials, including aspects of their implementation, design, analysis, reporting, and interpretation. In this type of investigation, the unit of analysis is a primary source of information about a clinical trial (e.g., published reports, study protocols, or abstracts), with meta-research being a second layer of information that summarizes what is known from various primary sources. After the formulation of the primary research question, the methodology of meta-research resembles that of other research projects, with predefined eligibility criteria, exposure variables, primary and secondary outcomes of interest, and an analysis plan. This type of study usually provides a high-level picture of the literature on a specific topic, always accompanied by a critical evaluation of the methodology and/or the quality of reporting of the studies included. Because relatively few resources are consumed to produce meta-research, these studies offer a great opportunity for clinical scientists working in settings with limited resources. In this article, we present the principles of designing and conducting meta-research and use our experience to suggest recommendations on how to perform and how to report this type of potentially very creative study. IMPLICATIONS FOR PRACTICE: The term meta-research pertains to a type of study in which the unit of analysis is, in most cases, the publication of a clinical trial. This type of study usually provides a high-level picture of the literature on a specific topic, always accompanied by a critical evaluation of the methodology, design, and/or the quality of reporting of the studies included. Because relatively few resources are consumed to produce meta-research, these studies offer a great opportunity for clinical scientists who work in low-income countries. This article presents the principles of designing and conducting meta-research and proposes practical recommendations on how to perform and report this type of potentially very creative study.