Impact of RRP1B Variants on the Phenotype, Progression, and Metastasis of Cervical Cancer.

Metastasis is a key determinant of cancer progression, influenced significantly by genetic mechanisms. RRP1B, primarily a nucleolar protein, emerges as a suppressor of metastasis, forming alliances with various cellular components and modulating gene expression. This study investigates the involvement of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation in cervical cancer. Through a comprehensive analysis of 172 cervical cancer patients, we evaluated five RRP1B single nucleotide polymorphisms (SNPs) (rs2838342, rs7276633, rs2051407, rs9306160, and rs762400) for their associations with clinicopathological features and survival outcomes. Significant associations were observed between specific genetic variants and clinicopathological parameters. Notably, the A allele of rs2838342 was associated with reduced odds of advanced tumor size, worse prognosis, and, preliminarily, distant metastasis, while the T allele of rs7276633 correlated with a decreased risk of higher tumor size and worse prognosis. Additionally, the C allele of rs2051407 demonstrated protective effects against larger tumors, metastasis, and adverse prognosis. The rs9306160 C allele exhibited a protective effect against metastasis. The rs762400 G allele was significant for reduced tumor size and metastasis risk. Furthermore, the rs2838342 A allele, rs7276633 T allele, rs2051407 C allele, and rs762400 G allele were associated with improved overall survival, demonstrating their potential significance in predicting prognoses in cervical cancer. Linkage disequilibrium and haplotypes analysis enabled us to evaluate the collective effect of the analyzed SNPs, which was in line with the results of allelic models. Our findings underscore the clinical relevance of RRP1B SNPs as prognostic markers in cervical cancer, shedding light on the intricate interplay between genetic factors and disease-progression dynamics. This research provides critical insights for future investigations and underscores the importance of incorporating RRP1B SNP detection into prognostic-assessment tools for accurate prediction of disease outcomes in cervical cancer.

Digital Phenotyping for Monitoring and Disease Trajectory Prediction of Patients With Cancer: Protocol for a Prospective Observational Cohort Study.

BACKGROUND: Timely recognition of cancer progression and treatment complications is important for treatment guidance. Digital phenotyping is a promising method for precise and remote monitoring of patients in their natural environments by using passively generated data from sensors of personal wearable devices. Further studies are needed to better understand the potential clinical benefits of digital phenotyping approaches to optimize care of patients with cancer. OBJECTIVE: We aim to evaluate whether passively generated data from smartphone sensors are feasible for remote monitoring of patients with cancer to predict their disease trajectories and patient-centered health outcomes. METHODS: We will recruit 200 patients undergoing treatment for cancer. Patients will be followed up for 6 months. Passively generated data by sensors of personal smartphone devices (eg, accelerometer, gyroscope, GPS) will be continuously collected using the developed LAIMA smartphone app during follow-up. We will evaluate (1) mobility data by using an accelerometer (mean time of active period, mean time of exertional physical activity, distance covered per day, duration of inactive period), GPS (places of interest visited daily, hospital visits), and gyroscope sensors and (2) sociability indices (frequency of duration of phone calls, frequency and length of text messages, and internet browsing time). Every 2 weeks, patients will be asked to complete questionnaires pertaining to quality of life (European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30]), depression symptoms (Patient Health Questionnaire-9 [PHQ-9]), and anxiety symptoms (General Anxiety Disorder-7 [GAD-7]) that will be deployed via the LAIMA app. Clinic visits will take place at 1-3 months and 3-6 months of the study. Patients will be evaluated for disease progression, cancer and treatment complications, and functional status (Eastern Cooperative Oncology Group) by the study oncologist and will complete the questionnaire for evaluating quality of life (EORTC QLQ-C30), depression symptoms (PHQ-9), and anxiety symptoms (GAD-7). We will examine the associations among digital, clinical, and patient-reported health outcomes to develop prediction models with clinically meaningful outcomes. RESULTS: As of July 2023, we have reached the planned recruitment target, and patients are undergoing follow-up. Data collection is expected to be completed by September 2023. The final results should be available within 6 months after study completion. CONCLUSIONS: This study will provide in-depth insight into temporally and spatially precise trajectories of patients with cancer that will provide a novel digital health approach and will inform the design of future interventional clinical trials in oncology. Our findings will allow a better understanding of the potential clinical value of passively generated smartphone sensor data (digital phenotyping) for continuous and real-time monitoring of patients with cancer for treatment side effects, cancer complications, functional status, and patient-reported outcomes as well as prediction of disease progression or trajectories. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/49096.

Pathomorphological Manifestations and the Course of the Cervical Cancer Disease Determined by Variations in the TLR4 Gene.

Cervical cancer (CC) is often associated with human papillomavirus (HPV). Chronic inflammation has been described as one of the triggers of cancer. The immune system fights diseases, including cancer. The genetic polymorphism of pathogen recognition receptors potentially influences the infectious process, development, and disease progression. Many candidate genes SNPs have been contradictory demonstrated to be associated with cervical cancer by association studies, GWAS. TLR4 gene activation can promote antitumor immunity. It can also result in immunosuppression and tumor growth. Our study aimed to investigate eight selected polymorphisms of the TLR4 gene (rs10759932, rs1927906, rs11536898, rs11536865, rs10983755, rs4986790, rs4986791, rs11536897) and to determine the impact of polymorphisms in genotypes and alleles on the pathomorphological characteristics and progression in a group of 172 cervical cancer subjects with stage I-IV. Genotyping was performed by RT-PCR assay. We detected that the CA genotype and A allele of rs11536898 were significantly more frequent in patients with metastases (p = 0.026; p = 0.008). The multivariate logistic regression analysis confirmed this link to be significant. The effect of rs10759932 and rs11536898 on progression-free survival (PFS) and overall survival (OS) has been identified as important. In univariate and multivariate Cox analyses, AA genotype of rs11536898 was a negative prognostic factor for PFS (p = 0.024; p = 0.057, respectively) and OS (p = 0.008; p = 0.042, respectively). Rs11536898 C allele predisposed for longer PFS (univariate and multivariate: p = 0.025; p = 0.048, respectively) and for better OS (univariate and multivariate: p = 0.010; p = 0.043). The worse prognostic factor of rs10759932 in a univariate and multivariate Cox analysis for survival was CC genotype: shorter PFS (p = 0.032) and increased risk of death (p = 0.048; p = 0.015, respectively). The T allele of rs10759932 increased longer PFS (univariate and multivariate: p = 0.048; p = 0.019, respectively) and longer OS (univariate and multivariate: p = 0.037; p = 0.009, respectively). Our study suggests that SNPs rs10759932 and rs11536898 may have the potential to be markers contributing to the assessment of the cervical cancer prognosis. Further studies, preferably with larger groups of different ethnic backgrounds, are needed to confirm the results of the current study.

Laparoscopic sentinel lymph node mapping with indocyanine green in endometrial cancer: surgeon's learning curve (cumulative sum analysis).

OBJECTIVES: To evaluate surgeons' learning curves for laparoscopic sentinel lymph node biopsy in endometrial cancer. METHODS: A prospective observational study was performed at the Oncogynecology Center, Lithuanian University of Health Sciences Hospital, from March 2018 to October 2022. Participating surgeons had no previous experience of laparoscopic sentinel lymph node biopsy with indocyanine green tracer. Cumulative sum analysis was used to create learning curves for the performance of eight surgeons, based on a specific result over a time period. Two different cumulative sum plots were made for each surgeon: successful bilateral sentinel lymph node mapping and removal of sentinel lymph node specimens containing actual lymphatic tissue. RESULTS: 190 patients were included. The overall rate of sentinel lymph node mapping was 89.5%: successful bilateral mapping was achieved in 134 (70.5%) patients, while in 36 (19%) patients sentinel lymph nodes were mapped unilaterally. The bilateral detection rate significantly improved in later study periods (from 59.3% in the first year to 85.0% in the last year; p=0.03). Analysis of the performance of the surgeons for bilateral sentinel lymph node mapping showed that the cumulative sum plot crossed the H0 limit line after 13 consecutive successful bilateral sentinel lymph node biopsies, indicating an acceptable level of competence to achieve the bilateral detection rate of at least 75%. This was accomplished by only one surgeon after 30 surgeries. Analysis of the performance of the surgeons for identification and removal of specimens containing histologically confirmed lymphatic tissue showed that the cumulative sum plots crossed the H0 limit line after six consecutive successful sentinel lymph node removals. This was accomplished by most of the surgeons (5 of 8). CONCLUSION: At least 30 procedures of indocyanine green traced laparoscopic sentinel lymph node biopsy were needed to reach an acceptable level of competence for a bilateral sentinel lymph node detection rate of at least 75%. TRIAL REGISTRATION NUMBER: ACTRN12619000979156.

Smartphone sensors for evaluating COVID-19 fear in patients with cancer: a prospective study.

Objective: This study aimed to analyze the association between the behavior of cancer patients, measured using passively and continuously generated data streams from smartphone sensors (as in digital phenotyping), and perceived fear of COVID-19 and COVID-19 vaccination status. Methods: A total of 202 patients with different cancer types and undergoing various treatments completed the COVID-19 Fears Questionnaire for Chronic Medical Conditions, and their vaccination status was evaluated. Patients' behaviors were monitored using a smartphone application that passively and continuously captures high-resolution data from personal smartphone sensors. In all, 107 patients were monitored for at least 2 weeks. The study was conducted between August 2022 and August 2023. Distributions of clinical and demographical parameters between fully vaccinated, partially vaccinated, and unvaccinated patients were compared using the Chi-squared test. The fear of COVID-19 among the groups was compared using the Mann-Whitney and the Kruskal-Wallis criteria. Trajectories of passively generated data were compared as a function of fear of COVID-19 and COVID-19 vaccination status using local polynomial regression. Results: In total, 202 patients were included in the study. Most patients were fully (71%) or partially (13%) vaccinated and 16% of the patients were unvaccinated for COVID-19. Fully vaccinated or unvaccinated patients reported greater fear of COVID-19 than partially vaccinated patients. Fear of COVID-19 was higher in patients being treated with biological therapy. Patients who reported a higher fear of COVID-19 spent more time at home, visited places at shorter distances from home, and visited fewer places of interest (POI). Fully or partially vaccinated patients visited more POI than unvaccinated patients. Local polynomial regression using passively generated smartphone sensor data showed that, although at the beginning of the study, all patients had a similar number of POI, after 1 week, partially vaccinated patients had an increased number of POI, which later remained, on average, around four POI per day. Meanwhile, fully vaccinated or unvaccinated patients had a similar trend of POI and it did not exceed three visits per day during the entire treatment period. Conclusion: The COVID-19 pandemic continues to have an impact on the behavior of cancer patients even after the termination of the global pandemic. A higher perceived fear of COVID-19 was associated with less movement, more time spent at home, less time spent outside of home, and a lower number of visited places. Unvaccinated patients visited fewer places and were moving less overall during a 14-week follow-up as compared to vaccinated patients.

TIRAP Rs8177376, Rs611953, Rs3802814, and Rs8177374 Polymorphisms and Their Association with Cervical Cancer Phenotype and Prognosis.

Cervical cancer is one of the most common cancers in women worldwide, which is typically caused by human papillomavirus (HPV). Usually, the toll-like receptor (TLR) signaling pathways eliminate the virus from the organism, but in some cases, persistent infection may develop. Unfortunately, the mechanism of immune tolerance is still unclear. Therefore, this study aimed to analyze TIRAP rs8177376, rs611953, rs3802814, and rs8177374 polymorphisms and to identify their impact on cervical cancer phenotype and prognosis. This study included 172 cervical cancer patients. Genotyping was performed using the PCR-RFLP assay. Univariate and multivariate logistic regression and Cox's regression models were applied for statistical analysis. The results revealed that older age at the time of diagnosis was statistically linked with the rs8177376 T allele (OR = 2.901, 95% Cl 1.750-4.808, p = 0.000) and the rs611953 G allele (OR = 3.258, 95% Cl 1.917-5.536, p = 0.000). Moreover, the T allele of rs8177376 (OR = 0.424, 95% Cl 0.220-0.816, p = 0.010) was found to be statistically associated with the lower tumor grade. Thus, TIRAP polymorphisms might be employed in the future as potential biomarkers for determining the phenotype and prognosis of cervical cancer.

Mitochondria-related TFAM gene variants and their effects on patients with cervical cancer.

Cervical cancer is the fourth most common type of cancer in women worldwide, with high incidence and mortality rates, particularly in developing countries. There are human papillomavirus vaccines and cytological screening programs available; however, there are no molecular markers that would aid the prognosis of the course of the disease or prediction of the outcomes of the patients. The aim of the present study was to investigate the associations between single nucleotide polymorphisms (SNPs) of the mitochondrial transcription factor A (TFAM) gene (rs11006132, rs11006129, rs1937, rs16912174, rs16912202 and rs3900887), and the clinical parameters and tumor phenotype of patients with cervical cancer. DNA isolated from patients with cervical cancer (n=172) was used for genotyping using Real-Time PCR using TaqMan probes. It was revealed that the TFAM rs3900887 TT and AT genotypes were associated with a lower risk of developing larger tumors. The results showed an association between the rs3900887 SNP and tumor phenotype, indicating TFAM rs3900887 as a potential biomarker for tumor size in cervical cancer.

POLG Gene Variants in Cervical Cancer Patients and Their Associations with Clinical and Pathomorphological Tumor Characteristics.

Cervical cancer is one of the most common cancers in women worldwide. Human papillomaviruses are known to be the main, but not the only risk factor, of this cancer type. Despite all the knowledge on this cancer type, it is still a challenge to predict the course of the disease, and therefore, minimally invasive biomarkers are needed. This study aimed to analyze single-nucleotide variants in the POLG gene and assess the associations with tumor phenotype and patient outcome. A total of 172 cervical cancer patients were included in this study. Clinical and tumor data were gathered from medical records retrospectively. Single nucleotide variations were determined using TaqMan probes with Real-Time PCR. Significant associations between POLG rs3087374 and cervical cancer patients' tumor histological type, stage, and tumor size were determined. The CA genotype and A allele of rs3087374 increased the probability of adenocarcinoma histological tumor type, IIIA stage, and T3 tumor size compared to CC genotype and C allele, respectively. Furthermore, patients with AA genotype in rs2072267 had longer metastasis-free survival than those with the GG genotype. Our data suggest that mitochondrial polymerase gamma encoded by nuclear POLG gene is important for specific tumor phenotype formation and patient outcome in cervical cancer.

In vivo dose verification method in catheter based high dose rate brachytherapy.

In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was performed for the first treatment fraction only. These findings indicate potential for further average dose error reduction in catheter based brachytherapy by at least 2-3% in the case that catheter locations will be adjusted before each following treatment fraction, however it requires more detailed investigation.

Single vs. multiple fraction regimens for palliative radiotherapy treatment of multiple myeloma : A prospective randomised study.

PURPOSE: To compare the impact of a single fraction (8 Gy × 1 fraction) and multifraction (3 Gy × 10 fractions) radiotherapy regimens on pain relief, recalcification and the quality of life (QoL) in patients with bone destructions due to multiple myeloma (MM). PATIENTS AND METHODS: In all, 101 patients were included in a randomised prospective clinical trial: 58 patients were included in the control arm (3 Gy × 10 fractions) and 43 patients into the experimental arm (8 Gy × 1 fraction). The response rate was defined according to the International Consensus on Palliative Radiotherapy criteria. Recalcification was evaluated with radiographs. QoL questionnaires were completed before and 4 weeks after treatment. RESULTS: Pain relief was obtained in 81/101 patients (80.2%): complete response in 56 (69%) and partial in 25 patients (30.9%). No significant differences were observed in analgesic response between the groups. Significant factors for pain relief were female gender, age under 65, IgG MM type, presence of recalcification at the irradiated site. Recalcification was found in 32/101 patients (33.7%): complete in 17 (53.2%) and partial in 15 (46.2%). No significant differences were observed in recalcification between the groups. Significant factors for recalcification were Karnofsky index ≥ 60%, haemoglobin level ≤ 80 g/dl, MM stage II and analgesic response at the irradiated site. The QoL after radiotherapy was improved in the control group. CONCLUSION: The same analgesic and recalcification response was observed using two different radiotherapy regimens. Higher doses should be used to achieve a better QoL.

The impact of one fraction of 8 Gy radiotherapy in palliative treatment of multiple myeloma patients with painful bone destructions.

BACKGROUND/AIM: Radiotherapy is required to overcome pain and to promote recalcification in multiple myeloma (MM) patients. The aim of our prospective study was to evaluate the impact of one fraction of 8 Gy regimen in palliative treatment of MM. MATERIALS AND METHODS: Forty-six patients with MM and painful bone destructions were treated by 8 Gy single fraction regimen. The visual analog scale was used for evaluation of pain. Analgesic use was measured prior to and after radiotherapy (4, 12, and 24 weeks). Recalcification was evaluated with radiographs before and after radiotherapy at 1 and 3 months. Quality of life questionnaires were completed before and 4 weeks after treatment. RESULTS: Decrease of pain was observed in 78.3% cases: according to the international consensus on palliative radiotherapy criteria, 43.5% were found to be completely and 34.8% partially responsive. Reduction of analgesic use was present in 68.4% and complete cessation in 31.6%. Recalcification was present in 55%: a complete response was observed in 35% and a partial response in 20%. The side effects after treatment were of the first grade and reversible. CONCLUSION: One fraction of 8 Gy regimen is effective in palliative treatment of MM patients with painful bone destructions.

Duffy and kidd genotyping facilitates pretransfusion testing in patients undergoing long-term transfusion therapy.

OBJECTIVE: Conventional serologic typing of red blood cell systems other than ABO and RhD can be inaccurate and difficult to interpret in patients who have recently undergone blood transfusion. While molecular-based assays are not used routinely, the usefulness of genotyping was investigated in order to determine patients who may benefit from this procedure. MATERIALS AND METHODS: Blood samples were taken from 101 patients with haemato-oncological, chronic renal, or gastroenterological diseases and from 50 donor controls; the samples were tested for Fya and Fyb by applying serologic and genetic methods. All patients had received 3 or more units of RBCs during the last 3 months. An average of 6.1 RBC units were transfused per patient. The average length of time from transfusion until blood sampling was 24.4 days. The haemagglutination test was applied for serological analysis, and the restriction length polymorphism assay was used for genotyping. RESULTS: In total, 33 (32.7%) patients showed positive reactions with anti-Fya or anti-Fyb while being negative genetically. False-positive Fya results were found in 23 samples, and false-positive Fyb in 10 specimens. During the last 3 months, significantly more RBC units were transfused to patients with discrepant results than to those with accurate phenotyping/genotyping results: median of 5 (mean ± SE: 6.85±0.69) versus median of 4 (mean: 5.71±0.51), respectively (p=0.025). The median length of time after the last transfusion was 25 days (mean: 28.72±2.23 days) in the group with accurate phenotyping/genotyping results versus a median of 14 days (mean: 15.52±1.95 days) in the group with discrepant results (p=0.001). Phenotypes and genotypes coincided in all donor samples. CONCLUSION: Genotyping assays for the Duffy system should be considered if the patient underwent blood transfusion less than 3 or 4 weeks before the sample collection. If the time frame from RBC transfusion exceeds 6 weeks, Duffy phenotyping can provide accurate results.

Reirradiation for patients with recurrence head and neck squamous cell carcinoma: a single-institution comparative study.

BACKGROUND AND OBJECTIVE: In the last decade, the number of publications that report on the use of external beam radiotherapy and high-dose-rate brachytherapy (HDR-BRT) in the treatment of recurrent head and neck cancer has increased, but no studies compare external beam radiotherapy and HDR-BRT. The aim of this study was to evaluate and to compare the efficacy and toxicity of the three-dimensional conformal radiotherapy (3D-CRT) and HDR-BRT in the treatment of recurrent head and neck cancer. MATERIAL AND METHODS: A total of 64 patients with head and neck cancer recurrence were randomly assigned at a 1:1 ratio to receive either 3D-CRT (50Gy/25 fractions) in the control group or HDR-BRT (30Gy/12 fraction) in the experimental group. RESULTS: The overall survival rate of patients treated with HDR-BRT at 1 and 2-years was 74% and 67%, respectively, compare to 3D-CRT group - 51% and 32%, respectively (P=0.002). Local control at 1- and 2-years in patients who received HDR-BRT was 77% and 63% compare with 47% and 25%, respectively, for the patients who received the 3D-CRT (P<0.001). Most patients developed mild to moderate acute mucositis and dermatitis. In the 3D-CRT group, severe late toxicity was determined in 11 patients (35.5%), and in the HDR-BRT group, in 1 patient (3.1%) (P=0.001). There was no grade 5 toxicity. CONCLUSIONS: Following our results, we concluded that HDR-BRT is a more effective and safer treatment approach for head and neck cancer recurrences than 3D-CRT.

Comparison of implant quality between loose and intra-operatively linked iodine-125 seeds in prostate cancer brachytherapy.

From 2007 to 2010, 230 patients had iodine-125 seeds implanted (loose or intra-operatively linked into seed trains with variable seed-to-seed spacing). The primary aim was to evaluate differences in implant quality by comparing the intra-operative and post-implant dosimetry in patients treated with loose and intra-operatively linked seeds. The secondary aim was to evaluate the "learning curve" for the procedure. The following parameters were compared: the radiation dose to 90% of the prostate volume (D90), the radiation dose to 30% of the urethral volume (DU30), the percentage of the prostate volume receiving 100% or 200% of the prescribed dose (V100 or V200, respectively), the percentage of the rectal volume receiving 100% of the prescribed dose (VR100), and the homogeneity index (HI). We obtained the following results for loose vs. intra-operatively linked seeds: D90 (Gy), 184.7 ± 15.0 vs. 177.9 ± 12.7 (p = 0.002); V100 (%), 95.5 ± 2.4 vs. 94.9 ± 3.2 (p = 0.206); V200 (%), 35.1 ± 7.5 vs. 24.3 plusmn; 6,9 (p < 0.001); DU30 (Gy), 218.6 ± 24.1 vs. 197.4 ± 19.5 (p = 0.001); VR100 (cm³), 0.6 ± 0.47 vs. 0.3 ± 0.3 (p < 0.001); HI (%), 31.8 ± 7.3 vs. 44.0 ± 9.8 (p < 0.001). The advantages of intra-operatively linked seed implantation over loose seed implantation are a more homogeneous prostate dose and lower urethral and rectal doses. The disadvantage is a lower post-implant D90. Sufficient experience with the loose seed implantation procedure was obtained after the first 40 patients. There was essentially no learning curve when a new implantation method using intra-operatively linked seeds was subsequently initiated.

Primary epithelioid sarcoma of the neck: a rare case report.

This report presents a case of a neck epithelioid sarcoma in a 20-year-old man with poor prognosis. The patient underwent surgery followed by external beam radiotherapy and brachytherapy performed as a boost. The treatment was well-tolerated, and there was no local recurrence or distant metastasis.

Corticosteroid-responsive pulmonary toxicity associated with fludarabine monophosphate: a case report.

UNLABELLED: Fludarabine monophosphate is an effective drug for the treatment of lymphoid malignancies. Myelosuppression, opportunistic infections, and autoimmune hemolytic anemia are the most common side effects of fludarabine. Herein we report a 55-year-old female that presented with fever and dyspnea after completing her third cycle of FMD (fludarabine, mitoxantrone, and dexamethasone) chemotherapy for stage IV non-Hodgkin follicular lymphoma. Chest X-ray revealed bilateral pneumofibrotic changes and chest CT showed bilateral diffuse interstitial changes with fibrotic alterations. No evidence of infectious agents was noted. The patient had a reduced carbon monoxide transfer factor (45%). Her symptoms and radiographic findings resolved following treatment with prednisolone. The literature contains several cases of fludarabine-associated interstitial pulmonary toxicity that responded to steroid therapy. Fludarabine-induced pulmonary toxicity is reversible with cessation of the drug and administration of glucocorticosteroids. CONFLICT OF INTEREST: None declared.

[Early postoperative intraperitoneal chemotherapy for the treatment of advanced gastric cancer]. / Skrandzio vezio gydymas ankstyvaja pooperacine intraperitonine chemoterapija.

UNLABELLED: Surgery remains the main treatment modality for gastric cancer. Adjuvant radiochemotherapy and adjuvant chemotherapy are becoming more and more popular in the treatment of advanced gastric cancer. Early postoperative intraperitoneal chemotherapy as one of the methods of adjuvant chemotherapy is currently being extensively investigated. The aim of the present study was to evaluate the toxicity of early postoperative intraperitoneal chemotherapy and its impact on postoperative complications as well as long-term survival. MATERIAL AND METHODS: A prospective study including 46 patients with gastric cancer who underwent radical resection was carried out during 2004-2005. Fourteen patients who received early postoperative intraperitoneal chemotherapy with 5-FU (EPIC group) were compared with 32 patients not receiving intraperitoneal chemotherapy (control group). All patient, except one patient in the EPIC group, received adjuvant radiochemotherapy or adjuvant chemotherapy. The toxicity of early postoperative intraperitoneal chemotherapy was evaluated using the WHO scale, and survival was estimated by the Kaplan-Meier method. RESULTS: The rate of postoperative complications was similar in both the groups (14.3% in the EPIC group vs. 12.5% in the control group). Four patients (28.6%) in the EPIC group developed grade III toxicity. There was no difference in survival comparing the EPIC group with the control group (median survival, 30 months and 34 months, respectively; P=0.500). CONCLUSIONS: Early postoperative intraperitoneal chemotherapy with 5-fluorouracile demonstrated acceptable toxicity and was relatively simple to perform. No survival benefit was documented combining early postoperative intraperitoneal chemotherapy with adjuvant radiochemotherapy or adjuvant chemotherapy.

Long-term results of high-dose-rate brachytherapy and external-beam radiotherapy in the primary treatment of endometrial cancer.

In this report we update our long-term follow-up results of the prospective study whose aim was to evaluate the efficacy of high-dose-rate (HDR) brachytherapy in combination with external-beam radiotherapy (EBRT) in the treatment of medically inoperable endometrial cancer. Between 1995 and 1998, 29 patients with stages I-III medically inoperable carcinoma of endometrium were treated with definitive irradiation. All patients underwent combined intracavitary HDR brachytherapy and EBRT. The EBRT dose was 50 Gy with midline shield from 16 Gy. The HDR brachytherapy dose was 50 Gy, delivered in 5 fractions in a weekly schedule. Overall survival (OS) at 5 and 10 years was 48.3% and 20.7%, respectively. Disease-specific survival (DSS) at 5 and 10 years was 73.5% and 67.9%, respectively. The 10-year DSS rate was 73.5% for all stages, 85.7% for Stage I disease, 71.4% for Stage II, and 16.7% for stage III disease. Late Grade 1-2 radiation complications were observed in 4 patients (13.8%). Our long-term follow-up confirms that HDR brachytherapy with EBRT appears to be an effective and safe treatment for stage I and II medically inoperable endometrial cancer.

[Review on the effectiveness of prostate cancer brachytherapy]. / Prostatos vezio brachiterapijos veiksmingumo apzvalga.

Ultrasound-guided transperineal prostate brachytherapy is now widely used modality in the treatment of prostate cancer. The overall prostate-specific antigen (PSA) progression-free survival at 10 years is 80-90% for low-risk patients. The results of long-term follow-up have showed better biochemical disease-free survival after I-125 and Pd-103 brachytherapy than after conventional external-beam radiotherapy and similar survival after radical prostatectomy. The most commonly reported dosimetric quantifiers include D90 (the dose that covers 90% of the prostate volume outlined on postimplant computed tomography images) and V100 (the fractional volume of the prostate that receives 100% of prescription dose). The biochemical disease-free survival correlates with the dose. In low-risk patients, achieving a D90 dose of 140-160 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a D90 dose higher than 200 Gy. In the immediate posttreatment period, the most common complication is acute urinary retention. Urinary symptoms such as frequency, nocturia, and dysuria occur commonly and are documented in about 80% of patients complaining of symptoms 2-3 months after treatment. Late urinary complications of brachytherapy include urethral stricture and incontinence. Incontinence is rare and mainly occurs in patients who had transurethral resection of the prostate either prior or after brachytherapy. Rectal complications (proctitis, rectal bleeding) are rare after prostate brachytherapy. Brachytherapy like external-beam radiotherapy but unlike surgery preserves ejaculation; potency rates also appear to be relatively high after brachytherapy, at 50-85%, and most patients' sexual quality and function are preserved. Since July 2007, the real-time I-125 prostate brachytherapy has been started in Lithuania and Baltic countries at the Hospital of Kaunas University of Medicine. A total of 150 low-risk patients (< or =T2a, Gleason < or =6, PSA < or =10) were treated by this method. Permanent prostate brachytherapy is an appropriate method for standard treatment of localized prostate cancer.

[Adjuvant therapy after curative resection with D2 lymphadenectomy for gastric cancer: results of a prospective clinical trial]. / Skrandzio vezio adjuvantinis gydymas po radikaliu operaciju su D2 limfadenektomija (perspektyviojo klinikinio tyrimo duomenys).

OBJECTIVE: Adjuvant chemoradiation for gastric cancer is used more frequently, but there is no general opinion about the effect of this treatment. The aim of this study was to compare adjuvant chemoradiation with adjuvant chemotherapy after radical operation for stomach cancer. MATERIAL AND METHODS: A total of 133 patients were included in this prospective study. Sixty-three patients after curative gastrectomy and D2 lymphadenectomy for gastric cancer were assigned to the chemoradiotherapy group and 70 to the chemotherapy group. The groups were identical by age, sex, and cancer stages. Toxicity was evaluated by the WHO scale, and survival was evaluated by the Kaplan-Meier method. RESULTS: Grade III and IV toxicity was found more frequently in the chemoradiation group than in the chemotherapy group (44.4% and 7.1%, respectively; P<0.0001). Treatment was not finished in 27% of patients in the chemoradiation group and 11.4% in the chemotherapy group (P=0.03). Overall survival was better in the chemotherapy group as compared with the chemoradiation group (P=0.039). Median survival for patients with stage III and IV cancer was 41 months in the chemotherapy group and 18 months in the chemoradiation group (P=0.085). Survival of patients with stage IIIA cancer in the chemotherapy group was significantly better (P=0.005). CONCLUSIONS: Median survival is shorter in the adjuvant chemoradiation group after curative gastrectomy for gastric cancer as compared with the adjuvant chemotherapy group. Adjuvant chemoradiation is more toxic and should be recommended only for patients with advanced-stage cancer.