Cervical Cancer in Sub-Saharan Africa: A Multinational Population-Based Cohort Study of Care and Guideline Adherence

BackgroundCervical cancer (CC) is the most common female cancer in many countries of sub‐Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS).MethodsOur observational study covered nine population‐based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44–125 patients diagnosed from 2010 to 2016 were selected in each. Cancer‐directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines.ResultsOf 632 patients, 15.8% received CDT with curative potential: 5.2% guideline‐adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow‐up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline‐adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I–III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36–8.37; HRR, 1.97; CI, 0.59–6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19–12.71) and no CDT (HRR, 9.43; CI, 3.03–29.33) showed substantially worse survival.ConclusionWe found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one‐fifth and possibly up to two‐thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients.Implications for PracticeDespite evidence‐based interventions including guideline‐adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population‐based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub‐Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub‐Saharan Africa to access timely and high‐quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer‐directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource‐constrained circumstances.     

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia

On November 5, 2020, a marketing authorization valid through the European Union (EU) was issued for acalabrutinib monotherapy or acalabrutinib in combination with obinutuzumab (AcalaObi) in adult patients with treatment‐naïve (TN) chronic lymphocytic leukemia (CLL) and also for acalabrutinib monotherapy in adult patients with relapsed or refractory (RR) CLL. Acalabrutinib inhibits the Bruton tyrosine kinase, which plays a significant role in the proliferation and survival of the disease. Acalabrutinib was evaluated in two phase III multicenter randomized trials. The first trial (ACE‐CL‐007) randomly allocated acalabrutinib versus AcalaObi versus chlorambucil plus obinutuzumab (ChlObi) to elderly/unfit patients with TN CLL. The progression‐free survival (PFS), as assessed by an independent review committee, was superior for both the AcalaObi (hazard ratio [HR], 0.1; 95% confidence interval [CI], 0.06–0.17) and acalabrutinib (HR, 0.2; 95% CI, 0.13–0.3) arms compared with the ChlObi arm. The second trial (ACE‐CL‐309) randomly allocated acalabrutinib versus rituximab plus idelalisib or bendamustine to adult patients with RR CLL. Also in this trial, the PFS was significantly longer in the acalabrutinib arm (HR, 0.31; 95% CI, 0.20–0.49). Adverse events for patients receiving acalabrutinib varied across trials, but the most frequent were generally headache, diarrhea, neutropenia, nausea, and infections. The scientific review concluded that the benefit‐risk ratio of acalabrutinib was positive for both indications. This article summarizes the scientific review of the application leading to regulatory approval in the EU.Implications for PracticeAcalabrutinib was approved in the European Union for the treatment of adult patients with chronic lymphocytic leukemia who have not received treatment before and for those who have received therapy but whose disease did not respond or relapsed afterward. Acalabrutinib resulted in a clinically meaningful and significant lengthening of the time from treatment initiation to further disease relapse or patient''s death compared with standard therapy. The overall safety profile was considered acceptable, and the benefit‐risk ratio was determined to be positive.     

Radiotherapy role in non-seminomatous germ cell tumors,radiobiological and technical issues of an unexplored scenario

International Journal of Clinical Oncology - Historically, non-seminomatous germ cell tumor (NSGCT) has been considered a radio-resistant disease, excluding radiotherapy (RT) from curative...     

Synthesis and pharmacological evaluation of novel conformationally constrained homologues of glutamic acid

Twelve novel conformationally constrained homologues of glutamic acid have been synthesized and pharmacologically characterized at ionotropic glutamate receptors (iGluRs). Synthesis of the target compounds involved 1,3-dipolar cycloaddition of nitrile oxides to suitable dipolarophiles. The structure to the compounds has been assigned by (1)H NMR and, in the case of derivatives (+/-)-4a, (+/-)-4b, (+/-)-5a, and (+/-)-5b, by means of an X-ray crystallographic analysis carried out on intermediate (+/-)-12a. The synthesized amino acids were found to be without affinity (K(i)/IC(50)>100microM) for iGluRs with the exception of compounds (+/-)-4b and (+/-)-5b, which showed a modest affinity for NMDA receptors (K(i)=34 and 13microM, respectively). The results indicate that the increased conformational constraints introduced by the cyclopropane ring and the spiro-attached proline ring are both detrimental to the pharmacological activity.     

Chlamydia pneumoniae and Mycoplasma pneumoniae in young children from China with community-acquired pneumonia

Eighty-five cases community-acquired pneumonia (CAP) in children 5 years or younger, confirmed by chest X-ray, and 185 age-matched control patients with diarrhea or dermatitis from the Outpatient Department at Beijing Children's Hospital were enrolled into this study. Nasopharyngeal swab specimens were obtained from all subjects. Real-time PCR-based fluorescence assays were performed for Chlamydia pneumoniae and Mycoplasma pneumoniae. A nested PCR was also run for C. pneumoniae for comparison of assays. C. pneumoniae was found in 3 (3.5%) of CAP cases and in 4 (2.1%) of controls (P = 0.51). M. pneumoniae was found in 6 (7.1%) of CAP cases and in none of the controls (P = 0.001). The agreement rate of the 2 applied PCR methods used for C. pneumoniae detection was 98.5%. Our study demonstrates that M. pneumoniae may play a significant role in CAP affecting children up to 5 years in China, whereas C. pneumoniae in nasopharyngeal specimens was not associated with CAP in this age group.     

Study of the diurnal variation of human lymphocyte subsets

The diurnal variation of peripheral white cells and in particular of different lymphocyte subsets has been investigated in 11 normal subjects. Monoclonal antibodies (Mab) phenotyping total T lymphocytes (UCHT1), cytotoxic/suppressor (UCHT4), helper T cells (Leu 3a), B lymphocytes (231) and K/NK cells (H25) have been used. In addition to the traditional parametric statistics, the chronobiological approach of cosinor was adopted in order to inferentially obtain the waveform covering the 24-hr period. Cosinor analysis validated the existence of a significant rhythm for leucocytes (p = 0.04, lymphocytes (p = 0.03), and Leu 3a positive cells (p = 0.04). The best fitting period was equal to 28 hr. No circadian rhythm was documented for lymphocyte subsets positive for Mab UCHT4, 231, H25, by testing the variability with a frequency ranging from 1 cycle every 12hr to 1 cycle every 28 hr. By the non-inferential analysis of temporal curves, a significant peak of Leu 3a positive cells at 20.00 hr (p less than 0.001) was observed. The acrophase has been recorded by cosinor analysis at 20.36 hr. We conclude that the circadian variability of Leu 3a positive cell profile must be taken into account when the helper/suppressor ratio is calculated. The time-dependence of this lymphocyte subpopulation suggests that when therapy with corticosteroids is considered in autoimmunity, it should be planned by keeping the peak of Leu 3a positive cells as a marker time.