Temporal changes in the cervical cancer burden in Bulgaria: Implications for eastern european countries going through transition

Publication date: October 2016
Source:Cancer Epidemiology, Volume 44
Author(s): Kaeli K. Samson, Gleb Haynatzki, Amr S. Soliman, Zdravka Valerianova
IntroductionIn most developed countries, incidence of cervical cancer declined likely due to well-established cervical cancer screening programs. However, such decline has not been identified in Eastern Europe, where such programs are not well established.MethodsThis study utilized data of the Bulgarian Cancer Registry for the period 1993–2013. Age-standardized incidence and mortality trends were analyzed using Joinpoint regression. Maps were created to illustrate spatial distributions of rates.ResultsThe northern region of Bulgaria showed a larger cervical cancer burden than the southern region and rural women tended to be diagnosed at older ages (p<0.0001) and later stages (p<0.0001) than urban women. The distribution of disease stages changed over the 21 years, with most common stages of diagnosis being stage II in 1993 (39.2%) to stage I in 2013 (44.7%; p<0.0001). While age-standardized mortality slightly increased over the 21 years (from 4.8 to 5.2 per 100,000; p=0.009), age-standardized incidence increased from 14.0 to 21.4 per 100,000 up until 2006 (p<0.001), after which it plateaued.ConclusionsThe lack of a similar plateau in mortality may be because the second most prevalent stage of diagnosis in recent years was stage III, indicating diagnosis at advanced symptomatic stages. Cervical cancer incidence is expected to continue to decrease if screening programs are strengthened and human papillomavirus vaccines are widely utilized. As Bulgaria has shared cervical cancer trends with other Eastern European countries in the past, it may be beneficial to develop future prevention interventions based on a regional, rather than a country-specific level.



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A case of metastatic renal cell carcinoma showing complete remission after cytoreductive nephrectomy followed by temsirolimus

Abstract

Here, we present a case report of a patient with poor-risk advanced renal cell carcinoma who had a complete remission after cytoreductive nephrectomy followed by temsirolimus. A 67-year-old woman was diagnosed with advanced renal cell carcinoma, stage pT3aN2M1 in April 2013. In the Memorial Sloan-Kettering Cancer Center criteria, she had three prognostic factors and was classified into the poor-risk category. After 23 weeks of treatment with temsirolimus, complete remission was achieved. Temsirolimus treatment was discontinued after 23 weeks because of grade 3 toxicity noninfectious pneumonitis. Five months after beginning steroid treatment without temsirolimus, a CT scan showed no new metastatic lesion or progression of disease. This was a very rare case with achievement of a complete remission after cytoreductive nephrectomy followed by temsirolimus.

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Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives

Abstract

Purpose

Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis.

Methods

A literature search was performed using the PubMed and MEDLINE databases. No publication time limit was set for article inclusion.

Results

Here, we found that clinical management of intestinal mucositis and diarrhea is somewhat ineffective at reducing symptoms, possibly due to a lack of specific targets for modulation. We observed that IL-1β contributes to the apoptosis of enterocytes in mucositis induced by 5-FU. However, 5-FU-related mucositis is far less thoroughly investigated with regard to specific molecular targets when compared to irinotecan-related disease. Several studies have proposed that a correlation exists between the intestinal microbiota, the enterohepatic recirculation of active metabolites of irinotecan, and the establishment of mucositis. However, as reviewed here, this association seems to be controversial. In addition, the pathogenesis of irinotecan-induced mucositis appears to be orchestrated by interleukin-1/Toll-like receptor family members, leading to epithelial cell apoptosis.

Conclusions

IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated.

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Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience

Abstract

Background

Being overweight has been reported to induce hepatic dysfunction during cytotoxic chemotherapy. Severe hepatic dysfunction can also be observed during gefitinib monotherapy, leading to interrupted or discontinued treatment. However, whether being overweight is a risk factor during gefitinib therapy is unknown.

Methods

We retrospectively reviewed 183 Japanese patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor-naïve non-small cell lung cancer (NSCLC) harboring EGFR mutations, who received gefitinib monotherapy between July 2007 and February 2014. We defined being overweight as having a body mass index (BMI) ≥ 25 kg/m² and assessed its potential relationship with ≥grade 2 hepatic dysfunction.

Results

The patient demographics were as follows: 114 women; median age 72 years (range 42–95 years); BMI ≥ 25 kg/m², n = 32; performance status 0–1, n = 136; stage IIIB/IV, n = 141; and major EGFR mutations, n = 171. Hepatic dysfunction ≥grade 2 during the gefitinib therapy was observed in 44 (24.0 %) patients, 22 (50.0 %) of whom interrupted or discontinued treatment. The median duration from gefitinib administration to the development of hepatic dysfunction was 56 days (range 6–1,352 days). Overweight patients were more likely to develop hepatic dysfunction ≥grade 2 compared to non-overweight patients according to a multivariate analysis adjusted for several confounding factors (hazard ratio 2.24; 95 % confidence interval 1.01–4.95; p = 0.046).

Conclusion

These results suggest that being overweight may induce hepatic dysfunction during gefitinib monotherapy in Japanese patients with EGFR-mutated NSCLC.

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Grid-Independent Descriptors (GRIND) analysis and SAR Guided Molecular Docking Studies to Probe Selectivity Profiles of Inhibitors of Multidrug Resistance Transporters ABCB1 and ABCG2.

Grid-Independent Descriptors (GRIND) analysis and SAR Guided Molecular Docking Studies to Probe Selectivity Profiles of Inhibitors of Multidrug Resistance Transporters ABCB1 and ABCG2.

Curr Cancer Drug Targets. 2016 Aug 31;

Authors: Shafi T, Jabeen I

Abstract
ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are major determinant of pharmacokinetic, safety and efficacy profiles of drugs thereby effluxing a broad range of endogenous substances across the plasma membrane. Overexpression of these transporters in various tumors is also implicated in the development of multidrug resistance (MDR) and thus, hampers the success of cancer chemotherapy. Modulators of these efflux transporters in combination with chemotherapeutics could be a promising concept to increase the effective intracellular concentration of anticancer drugs. However, broad and overlapped specificity for substrates and modulators of ABCB1 and ABCG2, merely induce toxicity and unwanted drug-drug interactions and thus, lead to late-stage failure of drugs. Therefore, it is of great importance to identify specific 3D structural requirements for selective inhibition of ABCB1 and ABCG2 transport function. Towards this goal, GRID Independent Molecular Descriptor (GRIND) models of selective inhibitors of both transporters have been developed, using their most probable binding conformations obtained from molecular docking protocol. Our results demonstrated a dominant role of molecular shape and different H-bonding patterns in drug-ABCB1/ABCG2 selective interactions. Moreover, distinct distances of different pharmacophoric features from steric hot spots of the molecules provided a strong basis of selectivity for both transporters. Additionally, our results suggested the presence of two H-bond donors at a distance of 8.4-8.8 A° in selective modulators of ABCG2.

PMID: 27585695 [PubMed - as supplied by publisher]

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Radiothérapie conformationnelle avec modulation d’intensité des cancers des voies aérodigestives supérieures : dose de tolérance des tissus sains. Muscles constricteurs du pharynx et larynx

Publication date: Available online 3 September 2016
Source:Cancer/Radiothérapie
Author(s): P. Graff, V. Woisard, S. Racadot, J. Thariat, Y. Pointreau
Les troubles fonctionnels chroniques affectant le pharyngolarynx ont émergé parmi les effets secondaires radio-induits impactant la qualité de vie des patients atteints de cancer de la sphère ORL survivant à long terme. Plusieurs structures anatomiques impliquées dans le fonctionnement complexe de cette région ont été identifiées. Une limitation de la dose délivrée sur ces structures pourrait contribuer à réduire les risques d'œdème laryngé, de dysphonie et surtout de dysphagie. Quelques recommandations dosimétriques peuvent être émises, comme maintenir la dose moyenne aux constricteurs du pharynx en dessous de 50 à 55Gy, la dose moyenne délivrée au larynx sus-glottique en dessous de 40 à 45Gy et si possible la dose moyenne délivrée au larynx glottique en dessous de 20Gy. Une épargne des muscles du plancher de la bouche et de l'œsophage cervical serait également bénéfique. Néanmoins, la qualité des données bibliographiques ne permet pas de considérer de telles recommandations comme suffisantes. Il est préconisé de retenir une philosophie d'épargne maximale des structures suscitées, la qualité de couverture des volumes cibles tumoraux restant prioritaire.Radio-induced pharyngolaryngeal chronic disorders may challenge the quality of life of head and neck cancer long survivors. Many anatomic structures have been identified as potentially impaired by irradiation and responsible for laryngeal edema, dysphonia and dysphagia. Some dose constraints might be plausible such as keeping the mean dose to the pharyngeal constrictor muscles under 50 to 55Gy, the mean dose to the supra-glottic larynx under 40 to 45Gy and, if feasible, the mean dose to the glottic larynx under 20Gy. A reduction of the dose delivered to the muscles of the floor of the mouth and the cervical esophagus would be beneficial as well. Nevertheless, the publications available do not provide an extensive enough level of proof. One should consider limiting as low as possible the dose delivered to these structures without compromising the quality of irradiation of the target tumor volumes.



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Argumentaire clinique pour la radiothérapie guidée par imagerie par résonance magnétique

Publication date: Available online 3 September 2016
Source:Cancer/Radiothérapie
Author(s): P. Maingon
Le concept de radiothérapie guidée par l'image bénéficie du développement de l'imagerie par résonance magnétique (IRM), associée à ces différentes capacités d'analyse des tissus, comme la spectroscopie ou les études de diffusion. La mise à disposition d'un dispositif de repositionnement des patients faisant appel à l'imagerie par résonance magnétique représente une valeur ajoutée incontestable, ne délivrant aucune dose additionnelle au patient durant son traitement tout en optimisant les stratégies adaptatives grâce à son contraste supérieur à la scanographie pour les tissus mous. Ses avantages sont connus pour les tumeurs cérébrales, les cancers des voies aérodigestives supérieures, les tumeurs pelviennes et thoraciques, les cancers digestifs. La radiothérapie adaptative est un concept qui inaugure une étape nouvelle du développement de la radiothérapie moderne selon différentes modalités. Plusieurs solutions technologiques sont étudiées et proposées aux cliniciens afin de faire bénéficier les patients de ces avancées technologiques.The concept of image-guided radiotherapy benefits from the development of magnetic resonance imaging (MRI) associated with different capacities of tissue analyses such as spectroscopy or diffusion analysis. The production of devices allowing the repositioning of patients through MRI represents a strong added value without delivering any additional dose to the patient while the optimization of the adaptative strategies are facilitated by a better contrast of the soft tissues compared to the scanner. The advantages of MRI are well demonstrated for brain tumours, head and neck carcinomas, pelvic tumors, mediastinal malignancies, gastrointestinal tract diseases. Adaptative radiotherapy inaugurates a new area of radiotherapy with different modalities. Several technological solutions are provided or discussed allowing the patients to benefit from thses new technologies as soon as possible.



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