Raman imaging monitors the time-resolved response of A. thaliana to the artificial inhibition of PSII.

The short-term (0-96 h) response of A. thaliana to the oxidative stress induced by PSII inhibitor metribuzin was examined using Raman spectroscopy. Whole leaves of wildtype (WT, Col-0) and ros1 mutant were scanned and changes in carotenoids were examined. Strong differences in Raman intensity distributions between WT and ros1 were observed. A stronger decrease of carotenoid v1(C=C) band intensity across the leaf was observed in ros1 after 48 h of exposure to metribuzin. It can be assumed that higher sensitivity to oxidative stress in ros1 mutant results in significantly faster degradation of carotenoids.

Non-destructive insights into photosynthetic and photoprotective mechanisms in Arabidopsis thaliana grown under two light regimes.

Probing insights into understanding photosynthetic processes via non-invasive means has an added advantage when used in phenotyping or precision agriculture. We employed Raman spectroscopy and fluorescence-based methods to investigate both the changes in the photosynthetic processes and the underlying protective mechanisms on Arabidopsis thaliana wild-type (WT), and ros1, which is a mutant of a repressor of transcriptional gene silencing, both grown under low light (LL: 100 µmol m-2s-1) and high light (HL: 400 µmol m-2s-1) regimes. Raman imaging detected a lower carotenoid intensity after two weeks in those plants grown under HL, compared to those grown under the LL regime; we interpret this as the result of oxidative damage of ß-carotene molecules. Further, the data revealed a significant depletion in carotenoids with enhanced phenolics around the midrib and tip of the WT leaves, but not in the ros1. On the contrary, small necrotic zones appeared after two weeks of HL in the ros1 mutant, pointing to the starting oxidative damage. The lower maximum quantum yield of the photochemistry (Fv/Fm) in the WT as well as in the ros1 mutant grown in HL (compared to those in the LL two weeks post-exposure), indicates the HL partially inactivated photosystems. Chlorophyll a fluorescence imaging further showed high non-photochemical quenching (NPQ) in the plants grown under the HL regime for both the WT and the ros1 mutant, but the spatial heterogeneity of NPQ images was much higher in the HL-grown ros1 mutant. Fluorescence screening methods revealed significantly high values of chlorophyll proxies in the WT as well as in the ros1 mutant two weeks after in the HL compared to those under LL. The data generally revealed an increased accumulation of phenolics under HL in both the WT and ros1 mutant plants, but the proxies of anthocyanin and flavonols were significantly lower in the ros1 mutant than in the WT. The comparatively low accumulation of anthocyanin in the ros1 mutant compared to the WT supports the Raman data. We conclude that integrated use of these techniques can be efficiently applied for a better understanding of insights into photosynthetic mechanisms.

Genotype and soil substrate effects on the wood quality of poplar grown in a reclaimed lignite-mining area.

An understanding of the structural organisation and chemistry of the cell walls in woody tissues is crucial from the perspective of plant mechanical strength, water transportability, as well as subsequent commercial utilisation of the wood. Poplar trees (Populus sp.), grown on two reclamation substrates ("Humus" and "Sand") under the extreme soil conditions of an external coal mining spoil heap of the lignite mine in Belchatów (Central Poland), were examined. Conventional parameters - tree-ring width (TRW) and wood density (WD) resolved annually (years 2008-2017) were corroborated by a novel approach of Raman spectroscopic analysis. Annually resolved Raman spectroscopic data representing the lignin-to-cellulose ratio (Li/Ce) enabled to estimate trends of lignification. The above traits were obtained for the three poplar genotypes: H-275, Grandis, and Androscoggin to assess the suitability of their plantation on the reclaimed heap. Our results show a significant effect of genotype on TRW, WD, and the Raman Li/Ce, while the effect of the soil substrate was less pronounced. The highest Li/Ce was identified in the H-275 genotype grown on a substrate with hummus. H-275 also showed higher TRW values compared to the other genotypes. WD was significantly higher in Grandis and Androscoggin genotypes grown on the "Sand" substrate. Associations between tree-ring parameters and climatic variables (temperature and precipitation) were mostly low and not statistically significant. Our findings from individual tree rings indicate that the genotype is the crucial factor influencing the lignification of poplar trees grown on post-mining lands.

Peritoneal carcinomatosis of colorectal origin treated by cytoreductive surgery and hyperthermic intraoperative peritoneal chemotherapy at the Bulovka University Hospital.

INTRODUCTION: Peritoneal carcinomatosis (PK) of colorectal origin is a malignant tumour of the peritoneum caused by spreading of colorectal carcinoma (KRK) over the peritoneal surface of the abdominal cavity and its organs. PK occurs as a synchronous tumour in 1520% of patients, and as metachronous disease in 2550% of patients. METHODS: A group of 66 patients operated on for PK was retrospectively evaluated; 18 patients were excluded due to insufficient data. We evaluated 48 patients in total (22 men and 26 women) with mean age of 58 and 53 years, respectively; 12 patients (25%) were aged over 65 years. The patients were operated on between 2000 and 2019 using the Sugarbaker´s method of maximal cytoreduction (CRS) + HIPEC (Hyperthermic Intraoperative Peritoneal Chemotherapy). We evaluated the length, median survival, the incidence of complications and lethality in relation to the Peritoneal Carcinoma Index (PCI) and the Completeness of Cytoreduction (CC) score. The patients were divided into two subgroups according to the PCI score (012 and >12, respectively) and the CC score (CC 01 and CC 23, respectively). RESULTS: The mean survival was 26.3 months in the group with PCI up to 12 and 21.4 months in patients with PCI above 12 (p=0.02). In the group with CC 01 the mean survival was 27.1 months, while in the patients with the CC 23 it reached 12.6 months (p=0.06). The morbidity rate requiring an intervention was 18.7% and the lethality rate was 6.25% in the entire group. The median survival of the entire group was 22 months (1334 months). CONCLUSION: Literary references and our results are comparable, confirming the high efficiency of this method both in our country and worldwide. The use of CRS and HIPEC, associated with acceptable mortality and morbidity in selected patients with PK of colorectal origin, results in a significant extension of overall survival (OS).

Pseudomyxoma peritonei (PMP) and its therapy - 20 years experience of a single surgical department.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare malignant disease with various grades of malignancy, producing mucinous and gelatinous masses. The origin of PMP is usually connected with the rupture of appendiceal mucinous tumours, other mucinous tumours of the gastrointestinal tract or of the ovary. The staging of this disease is determined by the PCI score (peritoneal cancer index), and the efficiency of surgical procedure by the CC score. Clinical presentation is very variable and depends on the stage of the disease. Many patients are asymptomatic with a minimal clinical finding, presented only with abdominal discomfort. A typical finding of the “jelly belly“ syndrome expands with progression of the disease. The diagnosis consists in preoperative determination of the tumour characteristics and PCI based on imaging methods, especially CT imaging. METHODS: The Sugarbaker technique of complete tumour removal or the so-called cytoreductive surgery (CRS) was used, including hyperthermic intraperitoneal chemotherapy (HIPEC) or alternatively early postoperative intraperitoneal chemotherapy (EPIC). We performed retrospective evalu-ation of 73 patients with pseudomyxoma peritonei undergoing surgery, 39 males and 34 females, mean age 50.6 and 56.4 years, respectively. Surgical revision was performed in 18 patients, 14 males and 4 females. The mean age of this group was 48.8 for the males and 47 for the females. The surgical procedures were performed between 1999 and 2018. Survival rates, median survival, complications based on Clavien-Dindo classification, lethality rates, and PCI and CC scores were assessed in the patient group. RESULTS: 96 surgeries were performed in 73 patients with pseudomyxoma peritonei at our surgical department between 19992018. The surgery had to be repeated in 18 patients (24.6%). High grade (HG) pseudomyxoma was diagnosed in 29 patients (39.7%), and low grade (LG) pseudomyxoma in 44 patients (60.3%). Overall morbidity was 27.3%, and the mortality rate was 5.4%. The mean overall survival (OS) was 139.5 months in the LG pseudomyxoma group and 71.5 months in the HG pseudomyxoma group. Median survival was 86 months in the entire group and 72 in the HG pseudomyxoma group; the median was not reached in the LG pseudomyxoma group. CONCLUSIONS: Results in the literature and our results are comparable, confirming the high efficiency of this method both in the world and in the Czech republic. The results indicate a highly statistically significant improvement of the OS with acceptable mortality and morbidity. These results confirm this method as a gold standard therapy for selected patients.

There is no correlation between signs of reflux laryngitis and reflux oesophagitis in patients with gastro-oesophageal reflux disease symptoms.

The objective of the present study was to determine if there is correlation between signs of reflux laryngitis (RL) and reflux oesophagitis (RE) in patients with gastro-oesophageal reflux disease (GORD) symptoms. Laryngeal photography obtained from patients during oesophagogastroduodenoscopy were examined by two otolaryngologists experienced in the field of extra-oesophageal reflux regarding the presence and severity of RL. The presence of RE was evaluated by gastroenterologist. Smokers, heavy drinkers and patients with bronchial asthma were excluded from the statistical analysis. A total of 681 patients were analysed. RL was diagnosed in 367 (53.9%) cases, of whom 182 patients had mild, 118 moderate and 67 severe (Reflux Finding Score > 7) RL. RE was diagnosed in 103 (28.1%) patients with RL and in 80 (25.7%) patients without RL. Neither the difference between the overall group of patients with RL and those without (OR 1.141, 95% CI 0.811-1.605, p = 0.448), nor the differences between the respective subgroups of patients with mild, moderate and severe RL and those without RL were statistically significant. The OR and 95% CI for mild, moderate and severe RL were 1.042, 95% CI 0.712-1.526, p = 0.834, 1.182, 95% CI 0.764-1.831, p = 0.453 and 1.0, 95% CI 0.566-1.766, p = 0.999 respectively. It can be concluded that there is no correlation between RL and RE in patients with GORD symptoms.

Contribution of ABCB1 and CYP2D6 genotypes to the outcome of tamoxifen adjuvant treatment in premenopausal women with breast cancer.

Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity.

Effect of certolizumab pegol over 96†weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure.

OBJECTIVE: Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. METHODS: RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. RESULTS: Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. CONCLUSIONS: CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. TRIAL REGISTRATION NUMBER: NCT01087788.

[Facial Disability Index and Facial Clinimetric Evaluation Scale: validation of the German versions]. / Facial Disability Index und Facial Clinimetric Evaluation Skala: Validierung der Deutschen Versionen.

BACKGROUND: A validated instrument to measure patient-related outcome and quality of life in facial palsy is not available in German language. METHODS: 2 appropriate questionnaires, the Facial Clinimetric Evaluation (FaCE) scale and the Facial Disability Index (FDI) were translated and validated according to international guidelines. The internal consistency of both German versions was assessed. The results of FaCE and FDI were correlated with results of the SF-36, the House-Brackmann scale and the Stennert index. RESULTS: 122 facial palsy patients with a median duration of 4.7 months were included. FaCE and FDI showed good to very good psychometric characteristics with Cronbach's alpha values between 0.667 and 0.907. Both questionnaires were able to distinguish different degrees of facial palsy. The comparison to the SF-36 shows the highest correlation with the subscale social function. DISCUSSION: The German versions of the FDI and FaCE are valid and should now be applied more frequently to assess the disease-specific quality of life in patients with facial palsy.

Miniaturized Raman instrumentation detects carotenoids in Mars-analogue rocks from the Mojave and Atacama deserts.

This study is primarily focused on proving the potential of miniaturized Raman systems to detect any biomolecular and mineral signal in natural geobiological samples that are relevant for future application of the technique within astrobiologically aimed missions on Mars. A series of evaporites of varying composition and origin from two extremely dry deserts were studied, namely Atacama and Mojave. The samples represent both dry evaporitic deposits and recent evaporitic efflorescences from hypersaline brines. The samples comprise halite and different types of sulfates and carbonates. The samples were analysed in two different ways: (i) directly as untreated rocks and (ii) as homogenized powders. Two excitation wavelengths of miniaturized Raman spectrometers were compared: 532 and 785 nm. The potential to detect carotenoids as biomarkers on Mars compared with the potential detection of carbonaceous matter using miniaturized instrumentation is discussed.

[Very late effects of radiotherapy -  limiting factor of current radiotherapy techniques]. / Velmi pozdní následky radioterapie -  limitující faktor soucasných radioterapeutických technik.

BACKGROUND: Very late effects of radiotherapy occur within decades after the initial exposure. Their development is induced by low doses of ionizing radiation (from 4 Gy per radiation series) and their clinical manifestations are difficult to distinguish from other independent diseases diagnosed in individuals not formerly treated with radiation. A long time period from the exposure confounds any causal relationships between radiation and adverse events. Still, these side effects not only reduce the patients quality of life but also lead to an early morbidity and mortality, hence generating significant costs in health care and social systems. PURPOSE: This article summarizes findings about the most common very late consequences of radiotherapy, which include cardiotoxicity, CNS toxicity, pneumotoxicity, renal toxicity and secondary malignancies. This issue is crucial in the group of children cancer patients, malignant lymphomas, testicular tumors and CNS tumors. Generally, the risk of very late effects of radiotherapy (RT) should be considered in all patients irradiated at a relatively early age with a high chance of long term survival. The risk of very late effects of RT is also one of the key limiting factors in the use of RT in the treatment of patients with benign lesions with longterm survival expectation, e. g. in patients with glomus tumors, neurofibromas, desmoid tumors or hemangiomas or other benign lesions (arterio venous malformations). Currently, the only known prevention of these very late adverse effects is to minimize the dose to critical structures to the lowest achievable level.

Palliative treatment of the advanced gastric cancer by means of surgery and HIPEC.

OBJECTIVES: We demonstrate a case report of the patient who suffered from advanced gastric cancer and was treated by means of surgery and HIPEC. BACKGROUND: Gastric cancer is a therapeutic challenge in the European countries due to late diagnosis, advanced stages of the disease in time of diagnosis and early recurrence in cases where a radical surgery is possible. METHOD: The patient with an advanced gastric cancer (pT3N2M1 - peritoneal and ovarian metastases) was treated by means of radical surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). Surgical treatment was followed by a standard chemotherapy. Due to recurrence, there was the second look surgery one year later again with HIPEC procedure. RESULTS: Patient survived 32 months after diagnosis and despite intraperitoneal recurrence she never developed clinically significant ascites and she never suffered from intestinal obstruction. CONCLUSION: This case demonstrate a potential benefit of new oncosurgical approach -radical surgery + HIPEC + EPIC in the treatment of gastric cancers (Tab. 2, Fig. 6, Graph 4, Ref. 18). Text in PDF www.elis.sk.

[Radiobiological pitfalls of new techniques in radiotherapy]. / Radiobiologická úskalí nových technik v radioterapii.

Radiotherapy techniques in the last decade evolved to the stage where the potential dose distribution significantly differs from earlier practices. Rotational IMRT, robotic radiotherapy or proton radiotherapy enables extremely precise dose delivery to target volumes, on the other hand, these techniques can yield a number of problems. As for photon radiotherapy, this concerns primarily the effect of large volume irradiation with doses of 0.10.5 Gy. In this range, the hypersensitivity to low doses and the bystander effect may play an important role. Proton therapy is upredictable in its radiobiological effect at the end of the Bragg curve and there is also uncertainty about the peaks exact location. These effects should be taken into account when choosing among the irradiation techniques or when applying tolerance doses to critical organs in clinical practice, especially in younger patients with long survival expectation.

[Registry of neuroendocrine tumors (NET) in Czech Republic after three years of data collection]. / Registr neuroendokrinních nádoru (NET) v CR po trech letech sberu dat.

BACKGROUND: Neuroendocrine tumors are traditionally considered to be "rare" diseases. On contrary, the prevalence of neuroendocrine tumors is high. Therefore, the diagnostics, treatment and follow-up of neuroendocrine tumors are subjected to an evolving interest. There are various specifics of neuroendocrine tumors requiring an appropriate feedback of each intervention i.e. data collection and central data evaluation. The "Cooperative Group for Neuroendocrine Tumors" (KSPNN) has been conducting a nationwide neuroendocrine tumors registry since June 2009. The first data summary after three years is aimed at evaluation of feasibility and data utility. MATERIAL AND METHODS: The anonymous data on diagnostics, therapy and follow up of patients with neuroendocrine tumors of any primary site are collected in the registry. The contribution is conditioned by morphologically proven diagnosis according to the current WHO 2010 classification, in earlier cases WHO 2000 classification. The registry is operated by the Institute of Biostatistics and Analyses, Masaryk University (Brno). The initial analysis includes data from June 2009 to October 2012. RESULTS: Data of a substantial share of neuroendocrine tumor carriers have been collected -  742 subjects with a valid record, i.e. about 14% of presumed prevalence. Moreover, the registry covers nearly one fourth of incidence in the period 2009- 2011. The morphological diagnoses with the sign of nonspecific "neuroendocrine tumors" comprise the majority of records (75%); the most frequent is "carcinoid tumor neuroendocrine tumors". This results in a clear requirement for more detailed specifications of morphology as well as separation of small cell (neuroendocrine) carcinoma possessing principal bio-logic differences to neuroendocrine tumors itself. There is an apparent polarity of recorded clinical stages. Both stage I and stage IV comprise 30% of the records. This result is presumably related to how the diagnosis is established, either early and incidentally in initial stage or late with a developed endocrine symptomatology, in advanced stage. There is an evident selection bias. The treatment data reflect current trends, dominance of surgical therapy including reasonable cytoreductive surgery, vast use of somatostatine analogues in advanced disease and persistent position of chemotherapy for high grade tumors. The distribution of treatment modalities in the records documents a certain adherence to international treatment standards (ENETS, ESMO, NCCN). CONCLUSION: The dynamics of data contributions confirm feasibility of data collection in the registry. The registry reveals a clear requirement for more detailed analyses of biopsies and more detailed disease morphology classification. In the near future, the registry is aimed to maintain the increasing volume of collected data and to cover the majority of neuroendocrine tumors incidence.

Peri-operative chemotherapy in patients with oesophageal and gastro-oesophageal junction cancer - three years of experience.

Peri-operative chemotherapy has been found to benefit patients with oesophageal and gastro-oesophageal junction adenocarcinoma. This study's aim was to evaluate the efficacy and tolerance of this treatment. The study included patients with carcinoma of the lower oesophagus and gastro-oesophageal junction in whom the disease was evaluated as potentially operable. Chemotherapy (CHT) consisted of three preoperative and three postoperative cycles of intravenous epirubicin and cisplatin on day 1 plus a continuous infusion of fluorouracil for 21 days (ECF) or oral capecitabine for 14 days (ECCap). Postoperative radio-chemotherapy (CRT) with fluorouracil or capecitabine after CHT was indicated in patients with two and more positive lymph nodes. Sixty-three patients started the treatment. Median follow-up was 32 months. Preoperative CHT was completed by 62 patients, 52 had surgery, 46 had radical resection, 25 patients had pN0 and 21 patient pN plus findings. Postoperative CHT was started in 39 (62%) patients and completed in 32 (51%). Ten (16%) patients had postoperative CRT. Adverse events of grade 3 and 4 were: neutropenia 17%, vomiting 8%, fatigue 5%, diarrhoea 3%. Reasons for omitting surgery in 11 (17%) patients were: progression in 7 patients, medically unfit in 3 patients, other in 1 patient. In the reporting period there were recurrences in 39 of all patients, in 7 locoregional only, in 10 distant plus locoregional, and in 19 distant metastases. Median survival was 24.1 months and 3-year survival rate was 42%. Peri-operative chemotherapy ECF/ECCap was feasible and well tolerated. Radical resection was performed in most patients.

[Which first-degree relatives of patients with colorectal neoplasias are at the highest risk]. / Kterí príbuzní prvního stupne nemocných s kolorektálními neoplaziemi jsou nejvíce ohrozeni.

BACKGROUND AND AIMS: The first-degree relatives of patients with colorectal neoplasias have higher risk of colorectal cancer than general population. The aim of our study was to identify first- degree relatives at the highest risk of colorectal neoplasia considering both their hereditary and nonhereditary risks. METHODS: We have analysed the results of colonoscopic examinations of the first- degree relatives done within the project and we have compared them with the epidemiologic data relevant to colorectal cancer that we obtained from first-degree relatives. RESULTS: 160 first- degree relatives (66 men, 94 women, mean age 48.2, SD ± 10.9 years) have undergone colonoscopic examination within the project, 105 (66 %) of them had no or nonneoplastic polyps, 55 (34 %) had neoplastic lesions. In the univariate analysis the risk factors for the occurrence of neoplastic lesions were: male sex (OR 2.30, 95% CI 1.18- 4.48, p = 0.014), age over 50 years (OR 2.78, 95% CI 1.42- 5.45, p = 0.003), sibship (OR 2.71, 95% CI 1.25- 5.87, p = 0.012), smoking (OR 2.37, 95% CI 1.21- 4.63, p = 0.012) and higher fat intake (OR 2.07, 95% CI 1.07- 4.04, p = 0.032). In the multivariate analysis only the age over 50 years proved significant (OR 2.84, 95% CI 1.32- 6.09, p = 0.007). The most of the neoplastic lesions in first- degree relatives were located in the right colon. CONCLUSIONS: We can confirm high prevalence of neoplastic lesions among first- degree relatives. First-degree relatives at the highest risk are men over 50 years of age, siblings, smokers, who do not reduce dietary fat intake. This group of patients share both genetic and environmental risks and thus should be screened with the highest priority.

Definitive radiochemotherapy with weekly cisplatin in patients with head and neck cancer; single institution outcome analysis.

PURPOSE: The objective of this study was to evaluate the feasibility, toxicity and efficacy of definitive radiochemotherapy with weekly cisplatin in head and neck cancer in a single institutional setting. METHODS: Previously untreated patients with stage II-IV head and neck cancer were included. Radiotherapy consisted of 70 Gy/7 weeks/35 fractions. All patients received concurrent cisplatin 40 mg/m(2) weekly. RESULTS: Between 2/2002 and 8/2009, 148 consecutive patients (WHO ≤ 2, male to female ratio 6/1, median age 56 years) were treated. The mean follow-up was 40 months. Tumors of the oropharynx were the most frequent (46%) and stage IV predominated (80%). Eighty-nine percent of the patients had received the full radiation treatment as planned. Omission of weekly cisplatin occurred frequently, mainly because of hematological toxicity. Only 64% of the patients completed at least 5 cycles of chemotherapy. Grade 3/4 mucosal toxicity developed in 32% of the patients. The late toxicities were acceptable: 74% of the patients were able to eat solid food during the 1st post-treatment year, 4 patients were not able to swallow at all during the 1st post-treatment year, requiring thus permanent feeding tube. Five cases of osteoradionecrosis of the mandible were reported. Three-year overall survival, locoregional control, time to progression and disease free survival were 34, 60, 52 and 29%, respectively. CONCLUSION: Definitive radiochemotherapy with weekly cisplatin was toxic, with high rate of morbidity and mortality in this patient population. Five weekly cycles of 40 mg/m(2) cisplatin seem to be the dose limit for most patients. Three-year survival was significantly reduced despite the promising high initial response and locoregional control.

Outcomes of patients with oesophageal cancer treated with preoperative chemoradiotherapy, followed by tumor resection: influence of nutritional factors.

PURPOSE: To assess the impact of clinical and nutritional factors on overall survival (OS) and time to disease progression of oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: We retrospectively studied and analysed several clinical and nutritional factors, such as performance status, weight changes before and during CRT, dysphagia, nutritional support, and serum albumin to see whether they exerted any impact on OS and time to disease progression. RESULTS: In 107 patients the average weight loss was 9.7% from the onset of signs of disease to the beginning of therapy and 3% during CRT. In univariate analysis, significant unfavorable impact on survival was proved for low performance status, severe dysphagia, need for nasogastric tube insertion, above-average weight loss before treatment, weight loss >5% during CRT, and serum albumin ≤ 35 g/l before or after CRT. Patients supported by oral nutritional supplements (ONS) had higher probability to attain full dosage of CRT and radical resection than did those obtaining dietary advice alone. In multivariate analysis, serum albumin level, nasogastric (NG) tube insertion and pretreatment body weight loss were independent prognostic factors for OS, while serum albumin level after CRT and NG tube insertion were prognosticators for time to progression. CONCLUSION: Serum albumin level can serve as a useful prognostic factor for the outcome of patients with oesophageal cancer treated with neoadjuvant CRT and surgery. Appropriate nutritional support of these patients increased the probability of attaining full dosage of CRT and radical disease resection.

Postoperative radiochemotherapy with weekly cisplatin in patients with head and neck cancer single-institution outcome analysis.

The objective of this study was to evaluate the feasibility, toxicity and efficacy of postoperative radiochemotherapy with weekly cisplatin in locoregionally advanced or high risk head and neck cancer in a single institutional setting. Patients with head and neck cancer of stage III/IV or patients with insufficient margins of resection were included in the study. Radiotherapy consisted of 70 Gy/ 7 weeks/ 35 fraction after R1/2 resection and 60-64 Gy/ 6-6,5 weeks/ 30-32 fraction after R0 resection, respectively. All patients received concurrent cisplatin 40 mg/m2 weekly. Between 7/2002 and 12/2008, 100 consecutive patients [WHO ≤ 2, male to female ratio 84/16, median age 54 years] were treated. Tumors of the oropharynx were the most frequent (49%) and stage IV was predominant (86%). 96% patients received the full radiation treatment as planned, median total tumor dose was 66 Gy. Omission of weekly cisplatin had been occurring frequently, the most frequent reason for its early cessation were hematological toxicities (34%). Grade 3/4 mucosal toxicity developed in 32%. No death was observed during the treatment. The late toxicities were acceptable, predominantly subcutaneous fibrosis and xerostomia in most of the cases. We recorded six cases of osteonecrosis. Two and half year overall survival, locoregional control, time to progression and disease free survival were 64%, 88%, 79% and 59%, respectively. Postoperative radiochemotherapy with weekly cisplatin is toxic, but tolerable and highly effective in terms of locoregional control and survival. Multivariete analysis revealed that the only prognostic factor for survival was primary surgery at the University centre.

Clinical activity of patupilone in patients with pretreated advanced/metastatic colon cancer: results of a phase I dose escalation trial.

BACKGROUND: New agents that are active in patients with metastatic colorectal cancer are needed. Patupilone (EPO906; epothilone B) is a novel microtubule-stabilising agent. METHODS: Patients with advanced colon cancer who progressed after prior treatment regimens received intravenous patupilone (6.5-10.0 mg m(-2)) once every 3 weeks by a 20-min infusion (20MI), 24-h continuous infusion (CI-1D) or 5-day intermittent 16-h infusion (16HI-5D). Adverse events (AEs), dose-limiting toxicities (DLTs), pharmacokinetics and anti-tumour activity were assessed. RESULTS: Sixty patients were enrolled. The maximum tolerated dose (MTD) was not reached in the 20MI arm (n=31), as no DLTs were observed. Three patients in the CI-1D arm (n=26) experienced 1 DLT each at 7.5, 8.0 and 9.0 mg m(-2), but MTD was not reached. However, the prolonged 16HI-5D arm was terminated at 6.5 mg m(-2) after two of the three patients developed a DLT. Diarrhoea was the most common AE and DLT, with increased severity at the higher doses (9.0 and 10.0 mg m(-2)). Grade 3 or 4 diarrhoea was observed in 11 (35%) of the patients in the 20MI arm, 4 (15%) of the patients in the CI-1D arm and 2 (67%) of the patients in the 16HI-5D arm. Patupilone activity was observed in the 20MI arm with a disease control rate of 58%, including four confirmed partial responses. The disease control rate in CI-1D arm was 39%. CONCLUSION: Patupilone given once every 3 weeks as a 20-min infusion had promising anti-tumour activity and manageable safety profile at doses that demonstrated therapeutic efficacy.