A Step Forward in Cancer Informatics—It Is Mandatory to Make Guidelines Machine Readable

Clinical guidelines are general recommendations for practicing clinicians regarding prevention, diagnosis and treatment of a given disease. One of the most comprehensive and used guidelines are developed and regularly updated by the National Comprehensive Cancer Network (NCCN). Guidelines are readily available for download in portable document format (PDF). A machine-readable representation of NCCN guidelines is currently not available. In this writing, we argue on the necessity that clinical guidelines should be published in a machine-readable format. After review of the available literature, we describe the most important achievements in the field. Publication of guidelines in a machine-readable form may also be beneficial for other scientific and technical disciplines

Quality-of-life and toxicity in cancer patients treated with multiple courses of radiation therapy

Background Treatment of metastatic cancer patients with multiple repeat courses of radiotherapy has become more frequent due to their improved overall survival. However, very little is known about their long-term outcome. This analysis reports on the quality-of-life, hematologic toxicity, patient-reported experiences and satisfaction, and psychological distress of cancer patients treated with multiple repeat radiotherapy. Methods All patients treated with ≥5 courses of radiotherapy between 2011 and 2019 at the Department of Radiation Oncology, University Hospital Zurich (USZ) were screened for this study. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. All patients completed two questionnaires: EORTC QLQ-C30 questionnaire for quality-of-life and a questionnaire evaluating psychological distress and patient-reported experiences. Hematologic toxicities were assessed via a recent blood sample. Results Of n = 33 patients treated with ≥5 radiotherapy courses and being alive, 20 (60.6%) participated in this study. The most common primary tumor was non-small cell lung cancer (n = 14, 42.4%). The most common sites of irradiation were brain (n = 78, 37.1%) and bone metastases (n = 59, 28.1%). All participating patients reported that they had experienced a subjective benefit from multiple repeat radiotherapy and denied increased side effects in later radiotherapy courses. Yet, 45% (n = 9) of the patients reported an increase of psychological distress with increasing numbers of radiotherapy treatments. While global health status was stable, patients having received multiple repeat radiotherapy reported increased fatigue (p = <0.006). Blood analysis showed significantly reduced hemoglobin and lymphocyte levels compared to the healthy population (p = <0.03). Discussion and conclusion Patient-reported experiences and satisfaction of long-term cancer patients treated with multiple repeat radiotherapy are positive. However, increased levels of fatigue and significantly reduced hemoglobin and lymphocyte levels were observed. These data indicate the need to further investigate the effects of multiple courses of radiotherapy in chronic cancer patients

Stereotactic body radiotherapy to defer systemic therapy in patients with oligorecurrent disease

Background Patients who develop oligorecurrent disease may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) to defer the start of systemic therapy and delay its potential side effects. We report oncological outcomes and patterns of failure in patients with oligorecurrent disease treated with SBRT and determine which factors impact the interval to initiation of systemic therapy. Material/Methods This retrospective study included patients with oligorecurrent disease (≤5 lesions) from any solid organ malignancy, treated with SBRT to all metastases and no systemic therapy for a minimum one month after SBRT between 01/2014 and 12/2019. The Kaplan-Meier method was used to analyze overall survival (OS) and progression-free survival (PFS), and the cumulative incidence of initiation of systemic therapy was analyzed assuming death without systemic therapy as a competing risk. Univariable and multivariable analyses are used to assess predictors of the systemic therapy-free interval. Results Among 545 patients treated with SBRT for oligometastatic disease, 142 patients were treated with SBRT only for oligorecurrent disease. The most common primary tumors were lung and gastrointestinal cancer in 47 (33.1 %) and 28 (19.7 %) patients, respectively. After a median follow-up of 25 months, the median PFS and OS was 6.1 months and 48.9 months, respectively. Distant metastases were the most common first failure, and oligometastatic distant failure occured in 86 patients (60.6 %). New metastases were treated with repeat SBRT in 48 patients (33.8 %). The 1- and 2-year cumulative incidence of initiation of systemic therapy was 24.6 % and 36.8 %, respectively. In multivariable analysis, the number of previous lines of systemic therapy and the cumulative volume of metastases were significantly associated with the interval to initiation of systemic therapy. Conclusion Selected patients with oligorecurrence achieved favorable OS and low cumulative incidence of initiation of systemic therapy. Prospective studies are warranted to determine how the deferral of systemic therapy impacts OS compared with immediate systemic therapy in combination with SBRT

Repeat stereotactic body radiotherapy for oligometastatic disease

BACKGROUND Patients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. MATERIALS/METHODS OMD patients treated with SBRT to 1-5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. RESULTS Among the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. CONCLUSION Despite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit

Stereotactic body radiotherapy for oligoprogression with or without switch of systemic therapy

BACKGROUND Oligoprogression is defined as cancer progression of a limited number of metastases under active systemic therapy. The role of metastasis-directed therapy, using stereotactic body radiotherapy (SBRT), is controversial as is the continuation versus switch of systemic therapy. We report outcomes of oligoprogressive patients after SBRT, and compare those patients that continued or switched their current line of systemic therapy. MATERIAL/METHODS We included patients who developed up to 5 progressive extracranial metastases under systemic therapy for any solid organ malignancy and were treated with SBRT to all lesions at our institution between 01/2014 and 12/2019. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and the interval to the next systemic therapy line determined using cumulative incidence functions. Multivariable Cox regression models were used to analyze the influence of baseline and post-progression variables on OS, PFS and survival with the next systemic therapy after SBRT. RESULTS Among 135 patients with oligoprogressive disease of which the most common primary tumor was lung cancer (n = 46, 34.1 %), 96 continued their current line of systemic therapy after oligoprogression. Among 39 who switched systemic therapy, 28 (71.8 %) paused or discontinued, while 11 (28.2 %) immediately started another systemic treatment. After a median follow-up of 27.2 months, patients that switched and those who continued systemic therapy after oligoprogression had comparable median OS (32.1 vs. 38.2 months, p = 0.47) and PFS (4.3 vs. 3.4 months, p = 0.6). The intervals to the next systemic therapy line were comparable between both cohorts (p = 0.6). An ECOG performance status of 2 and immediately starting a new systemic therapy after oligoprogression were associated with a poorer survival without next systemic therapy, while the de-novo OMD state was associated with better survival without next systemic therapy compared to the induced state. CONCLUSION Oncological outcomes of patients that continued or switched systemic therapy after SBRT for oligoprogression were comparable, potentially indicating that further lines of treatment may be safely delayed in selected cases

Evaluation of the prognostic value of the ESTRO EORTC classification of oligometastatic disease in patients treated with stereotactic body radiotherapy: A retrospective single center study

PURPOSE To explore the prognostic value of the oligometastatic disease (OMD) states as proposed by the European Society for Radiotherapy and Oncology (ESTRO) European Organisation for Research and Treatment of Cancer (EORTC) classification system. MATERIALS AND METHODS This retrospective single-institution study included patients with 1-5 extracranial metastases from any solid malignancy treated with SBRT to all metastases. OMD states were defined according to the ESTRO EORTC classification. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Discriminatory strength of the classification was assessed by Gönen & Heller's concordance probability estimate (CPE). Univariable and multivariable Cox regression models were used to assess predictors of OS and PFS. RESULTS In total, 385 patients were included. The median follow-up was 24.1 months. The most frequent OMD states were metachronous oligorecurrence (23.6%) and induced oligoprogression (18.7%). Induced OMD patients had significantly shorter median OS (28.1 months) compared with de-novo (46.3 months, p=0.002) and repeat OMD (50.3 months, p=0.002). Median PFS in de-novo OMD patients (8.8 months) was significantly longer than in repeat (5.4 months, p=0.002) and induced OMD patients (4.3 months, p<0.001). The classification system had moderate discriminatory strength for OS and PFS. Multivariable analyses confirmed that compared with induced OMD, de-novo was associated with longer PFS and repeat with longer OS. CONCLUSION All patients were successfully categorized according to the ESTRO EORTC classification system. The discriminatory strength of the classification was confirmed for OMD patients treated with metastases-directed SBRT. Larger multicenter trials are needed to validate the prognostic power for OMD patients irrespective of primary tumor and treatment approach

Clonal restriction and predominance of regulatory T cells in coronary thrombi of patients with acute coronary syndromes

Aims Regulatory T cells (Treg) exert anti-inflammatory and atheroprotective effects in experimental atherosclerosis. Treg can be induced against specific antigens using immunization strategies associated with clonal restriction. No data exist on Treg in combination with clonal restriction of T cells in patients with acute coronary syndromes (ACS). Methods and results Among T cell subsets characterized by flow cytometry, Treg (CD4+ CD25+ CD127low) were twice as frequent in coronary thrombi compared with peripheral blood. Treg prevailed among T cell subsets identified in coronary thrombi. To evaluate clonal restriction, genomic DNA was extracted from coronary thrombi and peripheral blood in order to evaluate T cell receptor (TCR) β chain diversity by means of Multi-N-plex PCR using a primer specific for all TCR β V gene segments and another primer specific for TCR β J gene segments. T cell receptor diversity was reduced in thrombi compared with peripheral blood (intra-individual comparisons in 16 patients) with 8 gene rearrangements in the TCR common in at least 6 out of 16 analysed coronary thrombi. Compared with age-matched healthy controls (n = 16), TCR diversity was also reduced in peripheral blood of patients with ACS; these findings were independent of peripheral T cell numbers. Conclusion We provide novel evidence for a perturbed T cell compartment characterized by clonal restriction in peripheral blood and coronary thrombi from patients with ACS. Our findings warrant further studies on Treg as novel therapeutic targets aimed at enhancing this anti-inflammatory component of adaptive immunity in human atherothrombosi

Patterns of metastatic spread and tumor burden in unselected cancer patients using PET imaging: Implications for the oligometastatic spectrum theory

INTRODUCTION AND BACKGROUND: Metastatic disease has been proposed as a continuum, with no clear cut-off between oligometastatic and polymetastatic disease. This study aims to quantify tumor burden and patterns of spread in unselected metastatic cancer patients referred for PET-based staging, response assessment of restaging. MATERIALS AND METHODS: All oncological fluorodeoxyglucose (FDG-) and prostate-specific membrane antigen (PSMA-) positron emission tomography (PET) scans conducted at a single academic center in 2020 were analyzed. Imaging reports of all patients with metastatic disease were reviewed and assessed. RESULTS: For this study, 7,000 PET scans were screened. One third of PET scans (n = 1,754; 33 %) from 1,155 unique patients showed presence of metastatic disease from solid malignancies, of which 601 (52 %) and 554 (48 %) were classified as oligometastatic (maximum 5 metastases) and polymetastatic (>5 metastases), respectively. Lung and pleural cancer, skin cancer, and breast cancer were the most common primary tumor histologies with 132 (23.8 %), 88 (15.9 %), and 72 (13.0 %) cases, respectively. Analysis of the number of distant metastases showed a strong bimodal distribution of the metastatic burden with 26 % of patients having one solitary metastasis and 43 % of patients harboring >10 metastases. Yet, despite 43 % of polymetastatic patients having >10 distant metastases, their pattern of distribution was restricted to one or two organs in about two thirds of patients, and there was no association between the number of distant metastases and the number of involved organs. CONCLUSION: The majority of metastatic cancer patients are characterized by either a solitary metastasis or a high tumor burden with >10 metastases, the latter was often associated with affecting a limited number of organs. These findings support both the spectrum theory of metastasis and the seed and soil hypothesis and can support in designing the next generation of clinical trials in the field of oligometastatic disease

Highly conformal combined radiotherapy with cisplatin and gemcitabine for treatment of loco-regionally advanced cervical cancer - a retrospective study.

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

Potential of ChatGPT in facilitating research in radiation oncology?

PURPOSE To evaluate the potential of the artificial intelligence (AI) chatbot ChatGPT in supporting young clinical scientists with scientific tasks in radio oncological research. MATERIALS AND METHODS Seven scientific tasks were to be completed in 3 hours by 8 radiation oncologists with different scientific experience working at a university hospital: creation of a scientific synopsis, creation of a research question and corresponding clinical trial hypotheses, writing of the first paragraph of a manuscript introduction, clinical trial sample size calculation, and clinical data analyses (multivariate analysis, boxplot and survival curve). No participant had prior experience with an AI chatbot. All participants were instructed in ChatGPT v3.5 and its use was provided for all tasks. Answers were scored independently by two blinded experts. The subjective value of ChatGPT was rated by each participant. Data were analyzed with regression-, t-test and Spearman correlation (p<0.05). RESULTS Participants completed tasks 1-3 with an average score of 50% and 4-7 with 56%. Scientific experience, number of original publications and of first/last authorships showed a positive correlation with overall scoring (p=0.01-0.04). Participants with little to moderate scientific experience scored ChatGPT to be more helpful in solving tasks 4-7 compared to more experienced participants (p=0.04), with simultaneously presenting lower scorings (p=0.03). CONCLUSIONS ChatGPT did not compensate for differences in scientific experience of young clinical scientists, with less experienced researchers believing false AI-generated scientific results