Clinical outcomes and patterns of severe late toxicity in the era of chemo-radiation for cervical cancer

Background: We present a comprehensive analysis of both therapy-induced severe late toxicity and outcome in a cohort of cervical cancer patients following radiation who were treated according to current guidelines and discuss the methodologic problems of systematically reporting these cases. We introduce a revised concept of reporting treatment failure. Patients and methods: The records of 128 cervical cancer patients who received radiation from 2003 to 2008 were reviewed. Results: Thirteen patients (10.2%) developed severe late toxicity. The combination of heavy smoking and cardiovascular diseases was found to be a significant contributing factor (HR 6.55, 95% CI 0.99-43.49, p=0.048). Thirty patients (23.4%) experienced treatment failure. Of these, 12 (9.4%) were defined to have persistent disease, and 18 (14.0%) developed recurrent disease. Patients with recurrent disease had significantly better survival time (p<0.001). Compared with the persistence subgroup, they had significantly more often multiple sites of relapse (66.7 vs. 8.3%, p=0.002) and the sites were more often diagnosed outside the pelvis (70.7 vs. 7.7%, p<0.001). Early disease stages (OR 4.46, 95% CI 1.87-10.63, p<0.001) and severe late toxicity (p=0.037) were found to be significant factors for an improved disease-free survival. Conclusions: A comprehensive depiction of both late therapy-related toxicity and treatment failure requires precise clinical descriptions and analyses of the clinical courses. Our new concept to differentiate treatment failure following radiotherapy in cervical cancer into persistent and recurrent disease permits a clear differentiation between distinct subgroups of patients with regard to prognosis and clinical presentation and will lead to a more precise description of these cases in the futur

Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

Purpose: The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS). Methods: We analyzed the overall courses of 85 unselected ROC patients and defined the following groups: A, platinum resistant patients (n=39); subgroup A.1, those who received no or at maximum one line of palliative chemotherapy (n=15, 38.5%); subgroup A.2, those who received≥two therapy lines (n=24, 61.5%); B, platinum sensitive patients, n=46. Results: Group A had significantly lower OS than group B (median: 16 vs. 25months; p=0.019). Group A.1 had significantly worse outcome compared to group A.2 (median: 5 vs. 21.5months; p<0.001). The comparison between study group A.2 and group B showed comparable survival rates (p=0.738). Considering only the patients who had completed treatment courses, the median number of therapy lines administered was higher in group A.2 than in group B (4 vs. 3; p=0.008). Conclusions: There is not only the known dichotomy between platinum sensitive and resistant ROC patients, but rather also within the platinum resistant subgroup itself. There is a considerably large subgroup of platinum resistant patients who will subsequently enter a phase where multiple treatment programs will be considered and administered. These patients have similar survival rates compared to those from the platinum sensitive patient group and the therapy principles of a chronic disease are applicabl

Suture Distension of Schlemm’s Canal in Canaloplasty: An Anterior Segment Imaging Study

Purpose. The object of this study was to investigate the role of the suture stent regarding its impact on reduction of intraocular pressure (IOP) in canaloplasty based on the distension of the inner wall of Schlemm’s canal. Methods. Nineteen glaucoma patients who underwent canaloplasty with successful positioning of the tensioning suture were included. The measurements were analyzed using linear mixed models, with the means adjusted to IOP, age, cup-to-disc ratio, and time of follow-up. Results. Mean follow-up time was 27.6 months (SD 10.5). Mean intraocular pressure (IOP) was 24.6 mmHg (SD 5.29), 13.8 (SD 2.65), and 14.5 (SD 0.71) before surgery, at 12 months, and at 36 months after surgery, respectively. 57.9% of patients had no medication at last evaluation. Differences and variations of measurements between the devices over a time of 12 months were not significant (p = 0.15 to 0.98). Some angles of distension associated with the suture stent inside SC were predictive for IOP reduction (p < 0.03 to < 0.001), but not for final IOP (p = 0.64 to 0.96). Conclusion. The angles of the inner wall of Schlemm’s canal generated by the suture stent were comparable between OCT and UBM and did not change significantly over time. There was a tendency towards a greater distension of Schlemm’s canal, when the difference was larger between pre- and postoperative IOP, suggesting the tensioning suture may contribute to IOP reduction

Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤80years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n=400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P=0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patient

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease

Purpose: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time. Methods: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n=70; group B 1998-2006, n=63). Results: Both study groups showed similar results in survival (median recurrent disease-specific survival—A 18 months vs. B 19 months; P=0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P=0.0057], received more therapy lines (≥3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P=0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A=−10.02; 95%CI −17.99 to −2.05; P=0.014). Conclusions: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfille

The effect of filtering on the two-global-flash mfERG: identifying the optimal range of frequency for detecting glaucomatous retinal dysfunction

Purpose: To study the effects of filtering bandwidth on the two-global-flash multifocal electroretinogram (mfERG) responses in primary open-angle glaucoma (POAG) compared with control subjects. Methods: A two-global-flash mfERG (VERIS 6.06™, FMS III) was recorded in 20 healthy subjects and 22 POAG patients with a band-pass filter (BPF) of 1-300Hz (103 Hexagons, M-sequence stimulus: Lmax 100cd/m2, Lmin0.5). This would suggest a filter setting of 10-300Hz for mfERG recordings in POAG. However, when a filter setting of 10-300Hz was compared to 1-300Hz, with a filter setting of 10-300Hz, the DC in POAG differed more (p0.5). Thus, we applied a filter setting of 1-200Hz, which seemed to be most sensitive in detecting glaucomatous retinal dysfunction (p<0.0001). Conclusions: A filter setting of 1-200Hz appears most sensitive to detect glaucomatous damage if using a two-global-flash mfERG: using a band-pass filter a with lower low-frequency cut-off, containing the 10Hz component, may be especially important in the small induced components that show glaucomatous damage most sensitively. High frequencies of 100-300Hz also contain information that differentiates glaucoma from normal and thus should be included in the analysi

Success and Failure of Primary Medical, Nonoperative Management In Breast Cancer

Background: Nonoperative but systemic therapy as first-line management is offered to some patients with breast cancer (BC) who have assumed limited life expectancy, such as older women or those who have distant metastases at initial presentation. We evaluated rates of and predicting factors for success and failure of this therapy approach. Methods: Seventy-five patients who were initially treated only systemically, and cases in which local control while avoiding surgery was the intended long-term therapy goal were analyzed. Additionally, two stage-dependent subgroups were distinguished (A: stage I-III, n=31; B: stage IV, n=44). Failure of therapy was defined as when secondary surgery had to be performed due to locoregional progression or in case of no surgery when severe locoregional clinical signs/symptoms were observed during the further course. Results: Patients in group A were older than those in group B (81 vs. 67.5years; P<0.001) and showed an increased survival (5-year rates: 40.2% vs. 24.3%). In 24 patients of the entire cohort (32%), secondary surgery had to be performed; surgery was performed more often in group A (58.1% vs. 13.6%). In the cases in which no surgery was performed (n=51), 11 women (21.6%) suffered from severe locoregional symptoms in the palliative situation (A: n=1; B: n=10). Although the presence of stage IV was a significant factor for therapy success (odds ratio (OR), 2.59; 95% confidence interval (CI), 0.95-7.05; P=0.039), skin involvement was associated with failure of therapy (OR, 3.57; 95% CI, 1.16-11.11; P=0.031). Conclusions: Nonoperative treatment may be offered to selected patients with BC who have assumed limited life expectancy. These women must be openly informed that this approach is not successful in nearly half of the case

Three-dimensional pathological size assessment in primary breast carcinoma

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P=0.0003, TV: P=0.0009, TSA: P<0.0001; multivariate analyses: MD: P=0.0018, TV: P=0.0109, TSA: P=0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alon

Predictive factors for preterm delivery under rural conditions in post-tsunami Banda Aceh

Objective: To assess the risk for preterm deliveries <37 week of gestation and associated prevalence of vaginal infection in a rural setting after the tsunami in Banda Aceh, Indonesia. Methods: Wet mount microscopy, vaginal pH and vaginal swabs for microbiological culture were collected in pregnant women during the 2nd trimester from February to June of 2005 in four temporary outpatient clinics and the patients were followed up until delivery. Results: One hundred and fifty-nine pregnant patients were screened. Sixty-two could be followed up until delivery. Thirty-nine (62.9%) delivered at term and 23 (37.1%) delivered prematurely. Significant risk factors for preterm delivery were a history of preterm delivery and group B streptococcus infection. Increased vaginal pH alone had no significant influence on preterm delivery, although there was a trend. Conclusion: The rate of preterm delivery was high in this cohort. We suggest risk stratification for preterm delivery in rural conditions by performing a vaginal pH and wet mount microscopy. If either is suspect we suggest collecting a vaginal swab for microbiological culture for targeted treatment. Patients with a history of preterm delivery are at increased risk and should be monitored closely

Comparison of Two Different OCT Systems: Retina Layer Segmentation and Impact on Structure-Function Analysis in Glaucoma

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP). Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student’s t-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP. Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 μm (SD 4.5) for MT and 9.8 μm (SD 5.4) for GCIPL (p<0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p<0.001). Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP