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• Circadian rhythm was previously shown to correlate with treatment toxicity. • Such findings could not be reproduced in this institutional cohort. • This is the first study investigating the impact of seasons on treatment toxicity. • Radiotherapy delivery in the darker half of the year yielded higher acute toxicity. The potential impact of the daytime and season of radiotherapy application on acute and late toxicity burden was analyzed on a cohort of curatively treated head and neck squamous cell carcinoma patients. Through a retrospective chart review, patient and tumor characteristics, treatment parameters and outcome were obtained. Patients treated with definitive or adjuvant radiotherapy with and without chemotherapy receiving ≥60 Gy between 2002 and 2015 were included (n = 617). Daily fraction times and dates were extracted. Median radiotherapy delivery time of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by the median day of the treatment course. Each year was divided into DARK and LIGHT by the March and September equinoxes. Acute (T) and late (A) toxicity were defined by TAME methodology. Median follow-up was 51 months. Mean T and A scores during and after radiotherapy in DARK vs. LIGHT were 1.98 vs. 1.61 (p = 0.0127) and 0.41 vs. 0.30 (p = 0.1699), respectively. Mean T and A scores during and after AM vs. PM radiotherapy were 1.71 vs. 1.88 (p = 0.0387) and 0.31 vs. 0.41 (p = 0.2638), respectively. Multivariate analyses indicated DARK vs. LIGHT as the only independent treatment time-related factor among other factors such as tumor subsite, UICC stage, radiotherapy technique, and chemotherapy for T. This is the first study investigating the impact of seasonality on toxicity burden, showing higher acute toxicity with radiotherapy in DARK. The daytime did not predict the toxicity. The hypothesis-generating findings of this retrospective study should be further investigated. [ABSTRACT FROM AUTHOR]

PURPOSE: Multidisciplinary cancer care is currently considered worldwide as standard for the management of patients with cancer. It improves patient diagnostic and staging accuracy and provides patients the benefit of having physicians of various specialties participating in their treatment plan. The purpose of this study was to describe the profile of patients discussed in the Tikur Anbessa Multidisciplinary Tumor Board (MTB) and the potential benefits brought by multidisciplinary care. METHODS: The study involved the retrospective assessment of all patient cases presented to the Tikur Anbessa Hospital colorectal cancers MTB between March 2016 and November 2017. The data were collected from the MTB medical summary documents and were analyzed using SPSS version 20 (SPSS, Chicago, IL). RESULTS: Of 147 patients with colorectal cancer, 96 (65%) were men. The median age at presentation was 46 years (range, 17-78 years). The predominant cancer was rectal (n = 101; 69%), followed by colon (n = 24; 16%). Of these, 68 (45%) and 22 (15%) had stage III and IV disease, respectively, on presentation to the MTB. The oncology department presented the majority of the patients for discussion. Most patients had undergone surgery before the MTB discussion but had no proper preoperative clinical staging information. The majority of patients with rectal cancer treated before the MTB discussion had undergone surgery upfront; however, most of the patients who were treatment naive before MTB received neoadjuvant chemoradiotherapy before surgery. CONCLUSION: Decisions made by tumor boards are more likely to conform to evidence-based guidelines than are those made by individual clinicians. Therefore, early referral of patients to MTB before any treatment should be encouraged. Finally, other hospitals in Ethiopia should take a lesson from the Tikur Anbessa Hospital colorectal cancers MTB and adopt multidisciplinary cancer management. [ABSTRACT FROM AUTHOR]

PURPOSE: Multidisciplinary cancer care is currently considered worldwide as standard for the management of patients with cancer. It improves patient diagnostic and staging accuracy and provides patients the benefit of having physicians of various specialties participating in their treatment plan. The purpose of this study was to describe the profile of patients discussed in the Tikur Anbessa Multidisciplinary Tumor Board (MTB) and the potential benefits brought by multidisciplinary care. METHODS: The study involved the retrospective assessment of all patient cases presented to the Tikur Anbessa Hospital colorectal cancers MTB between March 2016 and November 2017. The data were collected from the MTB medical summary documents and were analyzed using SPSS version 20 (SPSS, Chicago, IL). RESULTS: Of 147 patients with colorectal cancer, 96 (65%) were men. The median age at presentation was 46 years (range, 17-78 years). The predominant cancer was rectal (n = 101; 69%), followed by colon (n = 24; 16%). Of these, 68 (45%) and 22 (15%) had stage III and IV disease, respectively, on presentation to the MTB. The oncology department presented the majority of the patients for discussion. Most patients had undergone surgery before the MTB discussion but had no proper preoperative clinical staging information. The majority of patients with rectal cancer treated before the MTB discussion had undergone surgery upfront; however, most of the patients who were treatment naive before MTB received neoadjuvant chemoradiotherapy before surgery. CONCLUSION: Decisions made by tumor boards are more likely to conform to evidence-based guidelines than are those made by individual clinicians. Therefore, early referral of patients to MTB before any treatment should be encouraged. Finally, other hospitals in Ethiopia should take a lesson from the Tikur Anbessa Hospital colorectal cancers MTB and adopt multidisciplinary cancer management. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, the incidence of new cases of breast cancer is currently increasing resulting to high rates of morbidity and mortality. Breast cancer is by far the most common cancer accounting for more than one out of three cancer cases in women and one out of every five in the general population. The study was conducted in University of Gondar Hospital cancer center, located in the North-West Ethiopia; to evaluate the clino-pathologic characteristics of breast cancer and care provided for patients.Methods: All biopsy proven breast cancer patients treated between 2016 and 2017, were identified and information regarding histology, stage, therapeutic procedure and follow up was retrospectively collected from their individual medical records and descriptive analysis was done.Results: Among 82 patients treated, 67 (82%) were women and 15 (18%) were men. The median age at the time of diagnosis was 45 years (25-82 years). Operation was performed for 56 (68%) patients. The predominant histology was ductal carcinoma in 61 patients (74%), followed by breast carcinoma of No Special Type (NST) in 17 (21%). The late presentation of the patients and the advanced stage at the time of presentation was observed in most of the patients. Chemotherapy was administered in 79 (96%) patients. Radiotherapy was not available in the hospital.Conclusion: Breast cancer incidence is rising and becoming a major public health problem in Northern Ethiopia. Breast cancer care in northern-Ethiopia is limited in terms of both pathology, imaging and the offered treatment modalities, which need to be improved. [ABSTRACT FROM AUTHOR]

Background: Cisplatin and gemcitabine combined with conventional radiation therapy in the treatment of cervical cancer patients results in a favorable outcome but with excess toxicity. The purpose of this study was to evaluate the toxicity profile of dual chemotherapy and highly conformal external beam radiotherapy with image guided adaptive brachytherapy.Methods: Seventeen patients with cervical carcinoma FIGO stage IB2-IIIB were treated with curative intent between 2011 and 2015. A total dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Patients with 18FDG-PET/CT positive lymph nodes (n = 15; 83.3%) received an additional boost to a total dose of 62 Gy. Chemotherapy prescription goals were: concomitant during 5 weeks of external beam radiotherapy (EBRT) 40 mg/m2 cisplatin and 125 mg/m2 gemcitabine, followed by adjuvant chemotherapy from week 10 (2 cycles 50 mg/m2 cisplatin and 1000 mg/m2 gemcitabine). EBRT was followed by 3-4 fractions (6 Gy per fraction) of intrauterine image guided adaptive brachytherapy. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0).Results: One (6%) patient developed acute grade 3 diarrhea. We did not record any other acute or late gastrointestinal or urogenital toxicity higher that grade 3. Most common acute hematological toxicity was anemia grade 2 recorded in 10 (59%) patients. There was only one case of grade 3 neutropenia (6%). The number of patients that received the complete chemotherapy regimen was gradually declining during the course of therapy. From week 2 to 5, gemcitabine was omitted in 4 (24%),7 (41%), 8 (47%), and 12 (71%) patients respectively, similarly, cisplatin was omitted in 2 (12%),3 (18%),1 (6%) and 7 (41%) patients respectively. Adjuvant chemotherapy was omitted in 8 patients (47%). During a median follow-up time of 20 months (5 to 63 months) 6 (35%) patients developed disease relapse with 5 (29%) of them in the form of systemic disease.Conclusions: In contrast to previous findings cisplatin and gemcitabine in combination with highly conformal radiation therapy seems to have an acceptable toxicity profile. Further studies are needed to determine the optimal dosage of the proposed therapy concept. [ABSTRACT FROM AUTHOR]

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed. [ABSTRACT FROM AUTHOR]

Background: To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures.Methods: The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database.Results: In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %).Conclusion: Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future. [ABSTRACT FROM AUTHOR]

Purpose: Standard dose of external beam radiotherapy seems to be insufficient for satisfactory control of loco-regionally advanced cervical cancer. Aim of our study is to evaluate the outcome as well as early and chronic toxicities in patients with loco-regionally advanced cervical cancer, treated with dose escalated intensity modulated radiotherapy (IMRT) combined with cisplatin chemotherapy.Material and Methods: Thirty-nine patients with cervical carcinoma FIGO stage IB2 - IVA were treated with curative intent between 2006 and 2010. The dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Primary tumors < 4 cm in diameter (n = 6; 15.4 %) received an external beam radiotherapy (EBRT) boost of 5.4 Gy, primary tumors > 4 cm in diameter (n = 33; 84.6 %) received an EBRT boost of 9 Gy. Patients with positive lymph nodes detected with (18)FDG-PET/CT (n = 22; 56.4 %) received a boost to a total dose of 59.4 - 64.8 Gy. The para-aortic region was included in the radiation volume in 8 (20.5 %) patients and in 5 (12.8 %) patients the para-aortic macroscopic lymph nodes received an EBRT boost. IMRT was followed with a 3D planned high dose rate intrauterine brachytherapy given to 36 (92.3 %) patients with a total dose ranging between 15-18 Gy in three fractions (single fraction: 4-6.5 Gy). Patients without contraindications (n = 31/79.5 %) received concomitantly a cisplatin-based chemotherapy (40 mg/kg) weekly. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0).Results: Mean overall survival for the entire cohort was 61.1 months (±3.5 months). Mean disease free survival was 47.2 months (±4.9 months) and loco-regional disease free survival was 55.2 months (±4.4 months). 65 % of patients developed radiotherapy associated acute toxicities grade 1, ca. 30 % developed toxicities grade 2 and just two (5.2 %) patients developed grade 3 toxicities, one acute diarrhea and one acute cystitis. 16 % of patients had chronic toxicities grade 1, 9 % grade 2 and one patient (2.6 %) toxicities grade 3 in the form of vaginal dryness.Conclusion: Dose escalated IMRT appears to have a satisfactory outcome with regards to mean overall survival, disease free and loco-regional disease free survival, whereas the treatment-related toxicities remain reasonably low. [ABSTRACT FROM AUTHOR]

Purpose: Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry.Materials and methods: The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words.Results: A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleuraln = 4, limbn = 2, hepaticn = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia.Conclusions: In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia. [ABSTRACT FROM PUBLISHER]

Background: To evaluate toxicity and outcome of intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in patients with loco-regional advanced cervical cancer (LRACC). Methods: The study population comprised ten patients with 18FDG-PET\CT positive lymph nodes (LNs), who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary tumor received an additional external beam boost to a total dose of 55.8 Gy. A SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET\CT positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 – 18 Gy) was administered to the primary tumor. The primary goal of this study was to evaluate acute and early late toxicity and loco-regional control. Results: The median number of irradiated LNs per patient was 3 (range: 1–6) with a median middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was observed in 1 patient. Three of the patients developed a recurrence, one in the form of a local tumor relapse, one had a paraaortic LN metastasis outside the treated volume and the last one developed a distant metastasis. Conclusion: IMRT with SIB in the region of 18FDG-PET positive lymph nodes appears to be an effective therapy with acceptable toxicity and might be useful in the treatment of patients with locally advanced cervical cancer. [ABSTRACT FROM AUTHOR]

Background: This study was performed to evaluate the outcome after hemostatic radiotherapy (RT) of significant bleeding in incurable cancer patients. Methods: Patients treated by hemostatic RT between November 2006 and February 2010 were retrospectively analyzed. Bleeding was assessed according to the World Health Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 = clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding associated with fatality). The primary endpoint was bleeding at the end of RT. Key secondary endpoints included overall survival (OS) and acute toxicity. The bleeding score before and after RT were compared using the Wilcoxon signed rank test. Time to event endpoints were estimated using the Kaplan Meier method. Results: Overall 62 patients were analyzed including 1 patient whose benign cause of bleeding was pseudomyxoma peritonei. Median age was 66 (range, 37-93) years. Before RT, bleeding was graded as 2 and 3 in 24 (39%) and 38 (61%) patients, respectively. A median dose of 20 (range, 5-45) Gy of hemostatic RT was applied to the bleeding site. At the end of RT, there was a statistically significant difference in bleeding (p < 0.001); it was graded as 0 (n = 39), 1 (n = 12), 2 (n = 6), 3 (n = 4) and 4 (n = 1). With a median follow-up of 19.3 (range, 0.3-19.3) months, the 6-month OS rate was 43%. Forty patients died (65%); 5 due to bleeding. No grade 3 or above acute toxicity was observed. Conclusions: Hemostatic RT seems to be a safe and effective treatment for clinically and statistically significantly reducing bleeding in incurable cancer patients. [ABSTRACT FROM AUTHOR]

Background: Systematically screening published literature to determine the relevant publications to synthesize in a review is a time-consuming and difficult task. Large language models (LLMs) are an emerging technology with promising capabilities for the automation of language-related tasks that may be useful for such a purpose. Methods: LLMs were used as part of an automated system to evaluate the relevance of publications to a certain topic based on defined criteria and based on the title and abstract of each publication. A Python script was created to generate structured prompts consisting of text strings for instruction, title, abstract, and relevant criteria to be provided to an LLM. The relevance of a publication was evaluated by the LLM on a Likert scale (low relevance to high relevance). By specifying a threshold, different classifiers for inclusion/exclusion of publications could then be defined. The approach was used with four different openly available LLMs on ten published data sets of biomedical literature reviews and on a newly human-created data set for a hypothetical new systematic literature review. Results: The performance of the classifiers varied depending on the LLM being used and on the data set analyzed. Regarding sensitivity/specificity, the classifiers yielded 94.48%/31.78% for the FlanT5 model, 97.58%/19.12% for the OpenHermes-NeuralChat model, 81.93%/75.19% for the Mixtral model and 97.58%/38.34% for the Platypus 2 model on the ten published data sets. The same classifiers yielded 100% sensitivity at a specificity of 12.58%, 4.54%, 62.47%, and 24.74% on the newly created data set. Changing the standard settings of the approach (minor adaption of instruction prompt and/or changing the range of the Likert scale from 1–5 to 1–10) had a considerable impact on the performance. Conclusions: LLMs can be used to evaluate the relevance of scientific publications to a certain review topic and classifiers based on such an approach show some promising results. To date, little is known about how well such systems would perform if used prospectively when conducting systematic literature reviews and what further implications this might have. However, it is likely that in the future researchers will increasingly use LLMs for evaluating and classifying scientific publications. [ABSTRACT FROM AUTHOR]

Introduction: Documentation as well as IT-based management of medical data is of ever-increasing relevance in modern medicine. As radiation oncology is a rather technical, data-driven discipline, standardization, and data exchange are in principle possible. We examined electronic healthcare documents to extract structured information. Planning CT order entry documents were chosen for the analysis, as this covers a common and structured step in radiation oncology, for which standardized documentation may be achieved. The aim was to examine the extent to which relevant information may be exchanged among different institutions. Materials and Methods: We contacted representatives of nine radiation oncology departments. Departments using standardized electronic documentation for planning CT were asked to provide templates of their records, which were analyzed in terms of form and content. Structured information was extracted by identifying definite common data elements, containing explicit information. Relevant common data elements were identified and classified. A quantitative analysis was performed to evaluate the possibility of data exchange. Results: We received data of seven documents that were heterogeneous regarding form and content. 181 definite common data elements considered relevant for the planning CT were identified and assorted into five semantic groups. 139 data elements (76.8%) were present in only one document. The other 42 data elements were present in two to six documents, while none was shared among all seven documents. Conclusion: Structured and interoperable documentation of medical information can be achieved using common data elements. Our analysis showed that a lot of information recorded with healthcare documents can be presented with this approach. Yet, in the analyzed cohort of planning CT order entries, only a few common data elements were shared among the majority of documents. A common vocabulary and consensus upon relevant information is required to promote interoperability and standardization. [ABSTRACT FROM AUTHOR]

Background: The goal of this study is to evaluate the status and future perspectives of clinical trials on positron emission tomography in prostate cancer for diagnostic or therapeutic as well as for surveillance purposes.Methods: The www.ClinicalTrials.gov database was searched on the 20th of January 2017 for all trials containing terms describing "prostate cancer" (prostate, prostatic, malignant, malignancy, cancer, tumor) and "positron emission tomography". In total 167 trials were identified. Trials that included diseases other than PCa were excluded (n = 27; 16%). Furthermore, we excluded trials (n = 4, 2%) withdrawn prior to first patient enrollment. The remaining trials (n = 137, 82%) were selected for further manual classification analysis.Results: One hundred thirty-seven trials were detected and analyzed. Majority of trials were in "active" recruitment status (n = 46, 34%) followed by trials that had been "completed" - (n = 34, 25%) and trials with "closed recruitment but active follow-up" (n = 23, 17%). Phase 1 and 2 comprised 46% of the complete trial portfolio. Locally confined disease was of major interest (n = 46, 34%), followed by metastatic disease - not otherwise specified (n = 43, 13%). Evaluation of PET was the primary goal of the trial in 114 (83%) cases. Most of the trials evaluated only one agent (n = 122, 89%). Choline and PSMA represented two major groups (total 50%) and they were equally distributed across trial portfolio with 25% (n = 34) each. PSMA trials showed the highest average annual growth rate of 56%. The trials were conducted in 17 countries.Conclusion: The scientific community is showing a strong and ever-growing interest in the field and we expect that in the coming years, more phase III trials will be initiated ultimately delivering the required Level 1 evidence. [ABSTRACT FROM AUTHOR]

Background: To evaluate toxicity and outcome of intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in patients with loco-regional advanced cervical cancer (LRACC).Methods: The study population comprised ten patients with 18FDG-PET\CT positive lymph nodes (LNs), who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary tumor received an additional external beam boost to a total dose of 55.8 Gy. A SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET\CT positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 - 18 Gy) was administered to the primary tumor. The primary goal of this study was to evaluate acute and early late toxicity and loco-regional control.Results: The median number of irradiated LNs per patient was 3 (range: 1-6) with a median middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was observed in 1 patient. Three of the patients developed a recurrence, one in the form of a local tumor relapse, one had a paraaortic LN metastasis outside the treated volume and the last one developed a distant metastasis.Conclusion: IMRT with SIB in the region of 18FDG-PET positive lymph nodes appears to be an effective therapy with acceptable toxicity and might be useful in the treatment of patients with locally advanced cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: To investigate the adoption of machine learning in palliative care research and clinical practice, we systematically searched for published research papers on the topic. We found several publications that used different kinds of machine learning in palliative care for different use cases. However, on average, there needs to be more rigorous testing of the models to ensure that they work well in different settings. Objective: To summarize the available literature on using machine learning (ML) for palliative care practice as well as research and to assess the adherence of the published studies to the most important ML best practices. Methods: The MEDLINE database was searched for the use of ML in palliative care practice or research, and the records were screened according to PRISMA guidelines. Results: In total, 22 publications using machine learning for mortality prediction (n = 15), data annotation (n = 5), predicting morbidity under palliative therapy (n = 1), and predicting response to palliative therapy (n = 1) were included. Publications used a variety of supervised or unsupervised models, but mostly tree-based classifiers and neural networks. Two publications had code uploaded to a public repository, and one publication uploaded the dataset. Conclusions: Machine learning in palliative care is mainly used to predict mortality. Similarly to other applications of ML, external test sets and prospective validations are the exception. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the second commonly diagnosed cancer and the second leading cause of cancer death in women in Ethiopia, with rates among the highest worldwide. However, there are limited data on cervical cancer treatment patterns and survival in the country. Herein, we examine treatment patterns and survival of cervical cancer patients treated in Tikur Anbessa Hospital Radiotherapy Center (TAHRC), the only hospital with radiotherapy facility in the country.Methods: Women with histologically verified cervical cancer who were seen in 2014 (January 1, 2014 to December 31, 2014) at TAHRC were included. Information about clinical characteristics and treatments were extracted from the patients' medical record files. The information on vital status was obtained from medical chart and through telephone calls.Result: Among 242 patients included in the study, the median age at diagnosis was 48 years. The median waiting time for radiotherapy was 5.6 months (range 2 to 9 months). Stage migration occurred in 13% of patients while waiting for radiotherapy. Consequently, the proportion of patients with stage III or IV disease increased from 66% at first consultation to 74% at the initiation of radiotherapy. Among 151 patients treated with curative intent, only 34 (22.5%) of the patients received concurrent chemotherapy while the reaming patients received radiotherapy alone. The 5-year overall survival rate was 28.4% (20.5% in the worst-case scenario). As expected, survival was lower in patients with advanced stage at initiation of radiotherapy and in those treated as palliative care.Conclusion: The survival of cervical cancer patients remains low in Ethiopia because of late presentation and delay in receipt of radiotherapy, leading to stage migration in substantial proportion of the cases. Concerted and coordinated multisectoral efforts are needed to promote early presentation of cervical cancer and to shorten the unacceptable, long waiting time for radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a treatment option for patients with peritoneal metastases. We evaluated the current status of ongoing prospective clinical trials investigating PIPAC to provide an overview and predict trends in this field. Methods: All 367,494 records of clinical trials registered at ClinicalTrials.gov were searched for trials dealing with PIPAC. Active or unpublished trials were further analyzed. Results: In total, 22 clinical trials were identified and selected for further analyses. Most trials had a single-arm design and were phase I or II. No phase III trials were registered. Academic centers were recorded as primary sponsors in the majority of trials (63.6%). Every year, between 2 and 5 new trials were initiated. In 17 trials (81.8%), PIPAC was used in a palliative setting only, 2 trials performed PIPAC in a neoadjuvant setting, and 2 trials performed PIPAC in an adjuvant setting. Six different drugs (doxorubicin, cisplatin, oxaliplatin, nab-paclitaxel, 5-fluorouracil, and docetaxel) were used in these clinical trials. Most trials investigated the efficacy (n = 15) or safety (n = 7) of PIPAC therapies. Conclusions: The results of ongoing clinical trials will bring specific information on indications for PIPAC as well as the impact of PIPAC on quality of life and overall survival. [ABSTRACT FROM AUTHOR]

• Circadian rhythm was previously shown to correlate with treatment toxicity. • This is the first study investigating the impact of seasons on oncologic outcome. • Radiotherapy delivery in the darker half of the year yields better tumor control. The potential impact of daytime and season of radiotherapy application on prognosis is unclear. This was analyzed in a retrospective cohort of patients who were diagnosed with non-metastatic head and neck squamous cell carcinoma (HNSCC) and treated with definitive radiotherapy with or without chemotherapy. Patient and tumor characteristics, treatment parameters and outcome until last follow-up or death were obtained. Median radiotherapy delivery daytime of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by median date of treatment course. Each year was divided into DARK and LIGHT according to equinoxes. Time-to-event endpoints were defined by first biopsy confirming the HNSCC. Six hundred fifty-five cases were identified who were treated with (chemo)radiotherapy between 2002 and 2015. Median follow-up was 47 months. No significant heterogeneity in patient, tumor and treatment characteristics were observed between DARK and LIGHT or regarding median daily fraction time (X2 p > 0.05). Five-year loco-regional control (73% vs. 61%; p = 0.0108) and progression-free survival (51% vs. 43%; p = 0.0374) were superior when radiotherapy was administered in DARK. Neither the daytime nor any other treatment time-related parameter affected prognosis. This is the first study investigating and presenting the prognostic impact of seasonality regarding the treatment course on loco-regional control and progression-free survival (DARK > LIGHT). The biological mechanism of action is unclear. These results should be interpreted with caution and our findings have to be validated externally. [ABSTRACT FROM AUTHOR]

Decision making is one of the most complex skills required of an oncologist and is affected by a broad range of parameters. For example, the wide variety of treatment options, with various outcomes, side-effects and costs present challenges in selecting the most appropriate treatment. Many treatment choices are affected by limited scientific evidence, availability of therapies or patient-specific factors. In the decision making process, standardized approaches can be useful, but a multitude of criteria are relevant to this process. Thus, the aim of this review is to summarize common types of decision criteria used in oncology by focusing on 3 main categories: criteria associated with the decision maker (both patient and doctor), decision specific criteria, and the oftenoverlooked contextual factors. Our review aims to highlight the broad range of decision criteria in use, as well as variations in their interpretation. [ABSTRACT FROM AUTHOR]

Highlights • Recent guidelines from the ASCO and the BTS demonstrate significant discrepancies. • Ongoing trials in MPM are mostly in early phases and dominated by systemic therapies. • Very few trials evaluate loco-regional therapeutic approaches. • Current controversy surrounding local therapies will not be answered in the next years. Abstract Objectives Currently there are many uncertainties in the optimal treatment of malignant pleural mesothelioma (MPM), this is reflected in discrepancies between current guidelines. Our aim was to evaluate the current status of prospective interventional clinical trials within the ClinicalTrials.gov registry in MPM in order to predict a potential impact on MPM management in the next years. Material and Methods The records of 263.832 clinical trials registered were searched in December 2017. Trials starting between 2005 and 2017 (n = 262) were selected for further manual review. Trials including other tumour entities or mesothelioma originating outside the pleura (n = 94) were excluded, as well as trials where the primary endpoint has already been published (n = 22). Results In total, 91 clinical trials were identified and selected for further analysis. Most trials had a single arm design, were in phase I, and were non-randomized. Academic centres were recorded as primary sponsors in the majority of trials (56%), followed by industry in 21%. Most studies investigated targeted (n = 42) or cytotoxic therapies (n = 39). Ten studies investigated different genetic therapies. In 67% of the trials (n = 61) targeted and/or cytotoxic therapies were involved. Treatments involving surgery were investigated in 12 trials (13%), radiotherapy in 10 trials (11%). Only five studies (6%) were phase 3 studies and one was a phase 2/3 study. Four of these five phase 3 trials investigated targeted therapies, while one trial investigated prophylactic radiotherapy of operative tracts. Conclusions Currently running trials in MPM are mostly in early phases and dominated by systemic therapies. Very few trials evaluate loco-regional therapeutic approaches. The current controversy surrounding the use of surgery and radiotherapy within multimodal therapy strategies will not be answered by these trials in the coming years. [ABSTRACT FROM AUTHOR]

Objective: To report oncological outcomes and toxicity rates, of definitive platin-based chemoradiadiationtherapy (CRT) in the management of proximal esophageal cancer.Methods: We retrospectively reviewed the medical records of patients with cT1-4 cN0-3 cM0 cervical esophageal cancer (CEC) (defined as tumors located below the inferior border of the cricoid cartilage, down to 22 cm from the incisors) treated between 2004 and 2013 with platin-based definitive CRT in four Swiss institutions. Acute and chronic toxicities were retrospectively scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE-NCI v.4.0). Primary endpoint was loco-regional control (LRC). We also evaluated overall survival (OS) and disease-free survival (DFS) rates. The influence of patient- and treatment related features have been calculated using the Log-rank test and multivariate Cox proportional hazards model.Results: We enrolled a total of 55 patients. Median time interval from diagnosis to CRT was 78 days (6-178 days). Median radiation dose was 56Gy (28-72Gy). Induction chemotherapy (ICHT) was delivered in 58% of patients. With a median follow up of 34 months (6-110months), actuarial 3-year LRC, DFS and OS were 52% (95% CI: 37-67%), 35% (95% CI: 22-50%) and 52% (95% CI: 37-67%), respectively. Acute toxicities (dysphagia, pain, skin-toxicity) ranged from grade 0 - 4 without significant dose-dependent differences. On univariable analyses, the only significant prognostic factor for LRC was the time interval > 78 days from diagnosis to CRT. On multivariable analysis, total radiation dose >56Gy (p <0.006) and ICHT (p < 0.004) were statistically significant positive predictive factors influencing DFS and OS.Conclusion: Definitive CRT is a reliable therapeutic option for proximal esophageal cancer, with acceptable treatment related toxicities. Higher doses and ICHT may improve OS and DFS and. These findings need to be confirmed in further prospective studies. [ABSTRACT FROM AUTHOR]

Background: With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences.Methods: AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined.Results: AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17).Conclusions: Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended. [ABSTRACT FROM AUTHOR]

Background To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy. Methods Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses. Results The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V120 (urethral volume receiving ⩾120% of the PD; p = 0.0005) after multivariate Cox regression. Conclusions After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V120. GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent. [ABSTRACT FROM AUTHOR]

68Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative intended therapy. Owed to the novelty of the PSMA-targeting tracers, clinical evidence on the value of PSMA-PET is moderate but rapidly increasing. State of the art imaging is pivotal for radiotherapy treatment planning as it may affect dose prescription, target delineation and use of concomitant therapy.This review summarizes the evidence on PSMA-PET imaging from a radiation oncologist's point of view. Additionally a short survey containing twelve examples of patients and 6 additional questions was performed in seven mayor academic centers with experience in PSMA ligand imaging and the findings are reported here. [ABSTRACT FROM AUTHOR]

Background: To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy.Methods: Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses.Results: The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V120 (urethral volume receiving ≥120% of the PD; p = 0.0005) after multivariate Cox regression.Conclusions: After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V120. GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent. [ABSTRACT FROM AUTHOR]