Patterns of Care and Barriers to Utilization of Definitive Concurrent Chemoradiation Therapy for Stage III Non-Small Cell Lung Cancer in Russia.

BACKGROUND: Definitive concurrent chemoradiation (cCRT) is offered to only 3% of Russian patients with stage III NSCLC. To determine the patterns of care and barriers to cCRT utilization in Russia, we conducted a survey of practicing radiation oncologists (ROs). METHODS: Electronic IRB-approved survey containing 15 questions was distributed to Russian ROs. Fisher's exact test or Cochran-Armitage test of trend was used to assess the associations between clinical experience, practice type, and patterns of care. RESULTS: We analyzed 58 questionnaires completed by ROs-16 respondents from tertiary referral hospitals, and 42 from community or private centers. A total of 88% of respondents formulate treatment recommendations in multi-disciplinary tumor boards. For unresectable stage III NSCLC, the most common recommendation is sequential CRT (50%), followed by concurrent CRT (40%), with an observed higher utilization of cCRT in tertiary centers (9/16, 56% vs 14/42, 33%). Of the respondents, 31% do not offer cCRT to their pts. Among reasons for avoiding cCRT are (1) poor performance of pts (76%); (2) high toxicity of therapy (55%); (3) lack of consensus among tumor board members (33%); and (4) preference for sequential CRT (31%). Only 3% do not irradiate elective LNs. Eighty-six percent of respondents counsel their NSCLC pts regarding smoking cessation. CONCLUSIONS: Despite level 1 evidence, cCRT is rarely used in Russia for pts with locally advanced NSCLC, and preference for sequential therapy and concerns over high toxicity are the most common barriers. Education of Russian ROs may increase cCRT utilization, leading to improved survival, notably in the era of maintenance immunotherapy.

Phenological Analysis of Grasses (Poaceae) in Comparison with Aerobiological Data in Moscow (Russia).

Grasses (Poaceae) produce large amounts of pollen and are among the main causes of pollinosis worldwide. Despite their morphological similarity, pollen grains of different grass species may have different allergenicities. Therefore, quantification of the roles of individual species in airborne pollen is an important task. There are very few studies on this topic, and none of them have been conducted in a temperate continental climate. Our study was carried out for three years (2020-2022) in the urban territory of Moscow (Russia) and aimed to understand what grass species contribute the most to the total pollen load of the atmosphere. The comparison of aerobiological and phenological data was based on calculating the phenological index, which is a combination of phenological parameters, pollen productivity of individual species, and their abundance. Our data showed that the decomposition of pollination curves based on the phenological index was sometimes very efficient but not always possible in temperate continental climates. The main reasons for disagreement between aerobiological and phenological data were weather conditions and lawn mowing. Not all grasses were equally important as sources of allergenic pollen. The greatest contribution to the pollen load at the beginning of the season in Moscow was made by Dactylis glomerata, and to a lesser extent by Phleum pratense and Festuca pratensis. These are the most common species, which are widespread throughout Europe. The contribution of minor components is insignificant.

Aerobiological Monitoring and Metabarcoding of Grass Pollen.

Grass pollen is one of the leading causes of pollinosis, affecting 10-30% of the world's population. The allergenicity of pollen from different Poaceae species is not the same and is estimated from moderate to high. Aerobiological monitoring is a standard method that allows one to track and predict the dynamics of allergen concentration in the air. Poaceae is a stenopalynous family, and thus grass pollen can usually be identified only at the family level with optical microscopy. Molecular methods, in particular the DNA barcoding technique, can be used to conduct a more accurate analysis of aerobiological samples containing the DNA of various plant species. This study aimed to test the possibility of using the ITS1 and ITS2 nuclear loci for determining the presence of grass pollen from air samples via metabarcoding and to compare the analysis results with the results of phenological observations. Based on the high-throughput sequencing data, we analyzed the changes in the composition of aerobiological samples taken in the Moscow and Ryazan regions for three years during the period of active flowering of grasses. Ten genera of the Poaceae family were detected in airborne pollen samples. The representation for most of them for ITS1 and ITS2 barcodes was similar. At the same time, in some samples, the presence of specific genera was characterized by only one sequence: either ITS1 or ITS2. Based on the analysis of the abundance of both barcode reads in the samples, the following order could describe the change with time in the dominant species in the air: Poa, Alopecurus, and Arrhenatherum in early mid-June, Lolium, Bromus, Dactylis, and Briza in mid-late June, Phleum, Elymus in late June to early July, and Calamagrostis in early mid-July. In most samples, the number of taxa found via metabarcoding analysis was higher compared to that in the phenological observations. The semi-quantitative analysis of high-throughput sequencing data well reflects the abundance of only major grass species at the flowering stage.

Pollen Production of Selected Grass Species in Russia and India at the Levels of Anther, Flower and Inflorescence.

Grasses produce large amounts of pollen and are among the main causes of pollen allergy worldwide. Quantification of the roles of individual grass species in airborne pollen is an important task, because morphologically indistinguishable pollen grains of different species may differ in allergenicity. This requires knowledge of the pollen production of individual grass species; however, accumulated data are insufficient in this respect. Attempting to fill this gap, we studied pollen production per inflorescence in 29 grass species which are widespread in Middle Russia and India. Pollen production per inflorescence is determined by the number of grains per anther, the number of flowers in a spikelet and the number of spikelets per inflorescence, with the latter parameter being the most variable. We support the hypothesis that pollen production per inflorescence differs significantly between annual and perennial grasses. The greater pollen production of perennials can be interpreted as a tendency to guarantee cross-fertilization of species with self-incompatibility. The inferred pollen/ovule (P/O) ratios suggest the occurrence of facultative xenogamy in all annuals and obligate xenogamy in most perennials in the present dataset, though some self-incompatible annuals exist outside our sampling. Earlier data indicated that the P/O ratio of the annual cereal crop rye (Secale cereale) is higher than in any annual or perennial species sampled here. A ratio of pollen production to seed set (P/S ratio) is suggested to be another efficient parameter in reproductive biology of grasses. We highlight a need for detailed studies of reproductive biology in grasses that include both pollen and seed production. We found a correlation between pollen production per anther and anther length. A rough approximation of c. 1000 pollen grains per 1 mm of the length of an anther provides an instrument for estimates of pollen production in plant communities.

Gemcitabine combined with cisplatin as neoadjuvant chemotherapy in stage IB-IIIA non-small cell lung cancer.

This single-arm, multicenter, phase II study examined the objective response rate and toxicity after neoadjuvant chemotherapy with gemcitabine and cisplatin in patients with stage IB-IIIA non-small cell lung cancer. Treatment consisted of three 21-day cycles of gemcitabine (1000 mg/m(2)) on days 1 and 8 and cisplatin (75 mg/m(2)) on day 1 of each cycle. Surgery was performed 4-5 weeks after day 1 of the last cycle of study therapy. A total of 52 patients from five investigative sites in Russia were enrolled in the study, of which 50 (96.2%) received study therapy. Of the 49 patients who were evaluable for response, six (12.2%) had a complete response and 16 (32.7%) had a partial response, resulting in an overall response rate of 44.9%. Disease progression occurred in four out of the 49 (8.2%) patients. Radical tumor resection was performed in 38 out of the 49 (77.6%) patients. A total of 41 patients were assessed for a pathological complete response, of which four (9.8%) patients had pathological complete tumor regression. Postsurgical restaging was performed in 36 out of the 41 (87.8%) patients. Tumor downstaging occurred in 16 out of the 36 (44.4%) patients. Grade 3/4 neutropenia and thrombocytopenia were experienced by 28.0%/6.0% patients and 6.0%/2.0% patients, respectively. Grade 3 anemia occurred in 4.0% of the patients. Nonhematological toxicity was mild. Overall mortality was 30.0% (15 out of 50 patients), predominantly from progressive disease. The 1-year overall survival rate was 74.4% (95% confidence interval: 61.3-87.6%). Neoadjuvant chemotherapy with gemcitabine and cisplatin showed a good safety profile with an encouraging possibility of curative surgery in patients with early-stage non-small cell lung cancer.

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer.

BACKGROUND: Pemetrexed and carboplatin have demonstrated activity in breast cancer. Their potential synergism in experimental models and the proven efficacy of pemetrexed/platinum in other indications make pemetrexed/carboplatin an attractive combination in breast cancer. Thus, this two-stage, sequential, open-label, multicenter, phase II study assessed the efficacy and safety of pemetrexed plus carboplatin as first-line therapy in patients with locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients >or= 18 years with a histologic/cytologic diagnosis and no prior chemotherapy for LABC or MBC received pemetrexed 600 mg/m(2) and carboplatin AUC 5.0 on day 1 every 21 days with folic acid and vitamin B(12) supplementation. RESULTS: From June 2003 to April 2005, 50 patients with stage IIIB (30.0%) and stage IV (70.0%) disease were enrolled at 3 study centers. Twenty-eight percent of patients previously received adjuvant chemotherapy, 46.0% had visceral metastases, and 36.0% had >or=3 organs involved. Partial responses (RECIST criteria) were achieved in 27 (54.0%) patients (ORR = 54.0%; 95% CI, 39.3-68.2%). The median response duration was 11.1 months (95% CI, 6.5-14.0 months) and the median time to disease progression was 10.3 months (95% CI, 8.3-14.6 months). CTC hematologic toxicities were grade 3/4 neutropenia (58.0%/28.0%) and grade 3 thrombocytopenia (10.0%) and anemia (18.0%). Two (4.0%) patients had febrile neutropenia, 1 of whom died. No grade 4 non-hematologic toxicities occurred. Grade 3 non-hematologic toxicities were ALT (4.0%) and AST elevation, and edema, fatigue, pruritus, rash/desquamation, and renal toxicity (2.0% each). CONCLUSIONS: Results of this study suggest that the combination of pemetrexed and carboplatin has promising efficacy and an acceptable safety profile. Further assessment of this combination in a randomized trial of various breast cancer patient populations is warranted.

Medical Science Liaisons in Real-World Evidence Studies: Experience of AstraZeneca Russia.

There is no doubt that real-world evidence studies have the potential to improve and accelerate the development and delivery of safe and cost-effective innovative medicines to patients as well as influence the way we approach health and health care. Real-world evidence studies are a great challenge in terms of development and conduct, so there should be a good collaboration between the study team and clinical sites at all times, resulting eventually in timely and efficient enrollment. Engaging the sites and key external experts as early as possible during feasibility and routine visits, as well as highlighting the science rationale behind AstraZeneca's portfolio at investigator meetings and during medical science liaison (MSL) interactions, can create a positive impact on physician perception of a particular study and prioritization of patient recruitment in such studies. Therefore, we would like to underline the important role of MSLs in the risk-based monitoring setting of real-world evidence studies, with special attention to the studies with complicated patient profiles, tough timelines, and/or seasonal factors. This approach will be used further for other real world evidence projects of AstraZeneca Russia MC to ensure timelines and budget deliverables are met for the generation of high-quality evidence and eventually better health care for all of us.