Ulrike Schick

Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases.

Abstract Background. Substantial survival may be observed with oligometastatic prostate cancer. Combining androgen deprivation (AD) and high-dose external beam radiotherapy (RT) to isolated regional or distant lesions may be proposed for these patients and the outcome of this strategy is the purpose of the present report. Material and methods. From 2003 to 2010, 50 prostate cancer patients were diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM). Among the relapsing patients, the recurrence occurred after radical prostatectomy in 33 patients and curative RT (± AD) in 10 patients. The median age at diagnosis was 63 years (range, 48–82). All patients underwent a bone scan and 18F-choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing regional and/or distant nodal and bone and/or visceral metastases in 33 and 17 patients, respectively. The median delivered effective dose was 64 Gy. All but one patient received neo-adjuvant and concomitant AD. Results. After a median follow-up of 31 months (range, 9–89) the three-year biochemical relapse-free survival (bRFS), clinical failure-free survival, and overall survival rates were 54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved bRFS was found to be significantly associated with the number of OM. The three-year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was also correlated with a better three-year bRFS compared to lower doses: 65% vs. 41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy retained statistical significance (HR: 0.37, 95% CI 0.15–0.93). Conclusion. Oligometastatic patients may be successfully treated with short AD and high-dose irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment strategy may hypothetically succeed to prolong the failure-free interval between two consecutive AD courses.

Segmentation of Head and Neck Lymph Node Regions for Radiotherapy Planning Using Active Contour-Based Atlas Registration

In this paper, we present the segmentation of the head and neck lymph node regions using a new active contour-based atlas registration model. We propose to segment the lymph node regions without directly including them in the atlas registration process; instead, they are segmented using the dense deformation field computed from the registration of the atlas structures with distinct boundaries. This approach results in robust and accurate segmentation of the lymph node regions even in the presence of significant anatomical variations between the atlas-image and the patients image to be segmented. We also present a quantitative evaluation of lymph node regions segmentation using various statistical as well as geometrical metrics: sensitivity, specificity, dice similarity coefficient and Hausdorff distance. A comparison of the proposed method with two other state of the art methods is presented. The robustness of the proposed method to the atlas selection, in segmenting the lymph node regions, is also evaluated.

HPV-Related Oropharynx Cancer in the United Kingdom: An Evolution in the Understanding of Disease Etiology.

A rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) incidence has occurred throughout the developed world, where it has been attributed to an increasing impact of human papillomavirus (HPV) on disease etiology. This report presents the findings of a multicenter cross-sectional retrospective study aimed at determining the proportion of HPV-positive and HPV-negative OPSCC within the United Kingdom. Archival tumor tissue blocks from 1,602 patients previously diagnosed with OPSCC (2002-2011) were collated from 11 centers. HPV status was determined with three validated commercial tests to provide valid data for 1,474 cases in total. Corresponding national incidence data from the same decade were obtained from UK Cancer registries. The overall proportion of HPV+ OPSCC between 2002 and 2011 was 51.8% [95% confidence interval (CI), 49.3-54.4], and this remained unchanged throughout the decade [unadjusted RR = 1.00 (95% CI, 0.99-1.02)]. However, over the same period, the incidence of OPSCC in the broader UK population underwent a 2-fold increase [age-standardized rate 2002: 2.1 (95% CI, 1.9-2.2); 2011: 4.1 (95% CI, 4.0-4.3)]. Although the number of OPSCCs diagnosed within the United Kingdom from 2002 to 2011 nearly doubled, the proportion of HPV+ cases remained static at approximately 50%. Our results argue that the rapidly increasing incidence of OPSCC in the United Kingdom cannot be solely attributable to the influence of HPV. The parallel increase in HPV+ and HPV- cases we documented warrants further investigation, so that appropriate future prevention strategies for both types of disease can be implemented. Cancer Res; 76(22); 6598-606. ©2016 AACR.

Dose–response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancer

Dose-response curves (DRCs) and the quantitative parameters describing these curves were generated for grade 3 oral mucositis and dysphagia in 144 patients using individual patient DVHs. Curve fits to the oral mucositis clinical data yielded parameter values of mean dose in 2 Gy equivalent, MD(50) = 51 Gy (95% CI 40-61), slope of the curve, k = 1(95% CI 0.6-1.5). R(2) value for the goodness of fit was 0.80. Fits to the grade 3 dysphagia clinical data yielded parameter values of MD(50) = 44.5 Gy (95% CI 36-53), k = 2.6 (95% CI 0.8-4.5). R(2) value for the goodness of fit was 0.65. This is the first study to derive DRCs in patients receiving induction chemotherapy followed by chemo-radiation (IC-C-IMRT) for head and neck cancer. The dose-response model described in this study could be useful for comparing acute mucositis rates for different dose-fractionation schedules when using IMRT for head and neck cancer.

High-dose-rate brachytherapy boost to the dominant intra-prostatic tumor region: Hemi-irradiation of prostate cancer†

To assess the feasibility, toxicity, and outcome of prostate hemi‐irradiation with a high‐dose‐rate brachytherapy (HDR‐BT) boost for patients presumed to harbor dominant intra‐prostatic tumors in a single lobe.

Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

BACKGROUND AND PURPOSE Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning. MATERIALS AND METHODS Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models. RESULTS The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis. CONCLUSIONS The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature

PURPOSE To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

A study of the decision outcomes and financial costs of multidisciplinary team meetings (MDMs) in oncology.

Background:The benefits of multidisciplinary working in oncology are now accepted as the norm and widely accepted as being pivotal to the delivery of optimal cancer care. Central to this are the multidisciplinary meetings (MDMs) and we have evaluated decision outcomes and financial costs of these.Methods:We reviewed the electronic patient records of 551 newly referred patients, discussed at 14 tumour site-specific MDMs for adult solid tumours and lymphoma (paediatric oncology and acute leukaemia were excluded) over a 1-month period, a total of 52 MDMs were studied. In addition, the records of a further 81 patients from 10 different MDMs were reviewed where the treating consultant had clearly recorded their opinion of how the patient should be managed and this was compared with the final MDM’s consensus view. We also costed the MDMs utilising two different methodologies.Results:The mean age of the 551 patients in the study was 62 years. In all, 536 (97.3%) patients were treatment naive before MDM discussion and 15 (2.7%) had prior treatment. Median time to treatment after the MDM was 16 days. In 535 (97.1%) cases, the MDM discussions were clearly documented, 16 (2.9%) were not clearly documented. In total, 319 (57.9%) patients were discussed once, and 232 (42.1%) were re-discussed (one to six occasions). In 62 (12.7%) patients, there were delays in MDM discussion, 30 (48.4%) were related to radiology, 26 (41.9%) to histopathology and 6 (9.7%) a combination of both. Adherence to the MDM management plan decision occurred 503 times (91.3%) with 48 (8.7%) deviations. In the smaller cohort of 81 patients, the consultant management plan and MDM consensus was compatible 71 (87.6%) times. On four occasions, there were major alterations in management while six were minor. The cost per month of our MDMs ranged from £2192 to £10 050 (median £5136) with total cost of £80 850 per month and the cost per new patient discussed was £415.Conclusion:Adherence to MDM decisions by health-care professionals occurs in the majority of patients. MDMs are costly, which may have relevance in the currently challenged health-care financial environment. There is a need to improve MDM efficiency without losing the considerable benefits associated with regular MDMs.

Equivalence of cisplatin and carboplatin-based chemoradiation for locally advanced squamous cell carcinoma of the head and neck: A matched-pair analysis

BACKGROUND Carboplatin can be substituted for cisplatin in concomitant chemoradiation (CRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) when the latter is contraindicated. This matched-pair study aimed to compare the efficacy and acute toxicity of carboplatin and cisplatin. METHODS Patients treated with 2 cycles of concomitant carboplatin-based CRT were matched to patients treated with 2 cycles of cisplatin. Matching criteria included age, tumour site, stage, smoking status and use of induction chemotherapy. Radiation was delivered using conformal techniques. Data on weekly acute toxicity throughout CRT was compared using the chi-squared test for proportions. Kaplan Meier statistics described time to local relapse, distant relapse and overall survival, the log-rank test was used to compare 3-year survival outcomes. RESULTS Sixty-five patients who received carboplatin were matched to 65 who received cisplatin. Significant differences in toxicity included increased emesis with cisplatin and more anaemia and thrombocytopenia with carboplatin. There was no significant difference in 3-year locoregional control (87% vs. 79%, p=0.54), freedom from distant metastases (88% vs. 85%, p=0.79) and overall survival (59% vs. 68%, p=0.24) between the carboplatin and cisplatin cohorts, respectively. CONCLUSIONS When cisplatin is contraindicated, carboplatin-based CRT yields equivalent treatment outcomes in patients with LASCCHN.

Outcome and prognostic factors in endometrial stromal tumors: a Rare Cancer Network study

PURPOSE To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). METHODS AND MATERIALS A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. RESULTS Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administered to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age (≤60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I-II vs. III-IV). Positive lymph node staging had an impact on OS (p < 0.001). CONCLUSION The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines.