Prevalence of carotid plaque stenosis after head and neck radiotherapy - an observational study of 156 survivors.

Background: Radiotherapy for head and neck cancer (HNC) represents a well-known predisposing factor for asymptomatic carotid artery lesions and acute cerebrovascular accidents. Our aim is to provide contemporary estimates on the prevalence, severity, and characteristics of carotid artery lesions in HNC survivors. Patients and methods: We prospectively included HNC patients who underwent radiotherapy and were free from the disease at the time of duplex ultrasound evaluation. Patients were re-contacted telephonically and those who agreed to participate were invited for an ambulatory visit when the investigators collected clinical information and performed duplex ultrasound examination based on a predefined protocol. Results: A total of 156 patients were included and underwent duplex ultrasound examination after a mean of 65.2 months from the last session of radiotherapy. A total of 36 patients (23.1%) had normal carotid arteries; mild, non-stenotic lesions were observed in 49.4% (n = 77) of patients; severe stenotic plaques were found in 27.5% (n = 43) of patients. One patient found with an asymptomatic occlusion of the left ICA. The prevalence of major cardiovascular risk factors and high radiation dose increased proportionally with plaque severity. Low echogenicity plaque was found in 59 (37.8%) patients on the right side and 57 (36.5%) on the left side; long segment plaque in 49 (31.4%) patients on the right side and in 47 (30.1%) on the left side; an atypical location of the lesions in 42 (26.9%) patients on the right side and in 48 (30.8%) on the left side. Conclusions: The prevalence of occlusion and severe stenosis after radiotherapy for HNC was very low in our study population. Low echogenicity plaque, long segment plaque, and an atypical location were common findings. Classic cardiovascular risk factors appear to have had a causative role: a routine screening of radiotherapy-treated patients might be necessary only in patients with concomitant cardiovascular risk factors or exposed to high-dose neck radiation.

[Modern Treatment Concepts in Radiation Oncology]. / Moderne Behandlungskonzepte in der Radio-Onkologie.

Modern Treatment Concepts in Radiation Oncology Abstract. Radiotherapy is a widely used form of therapy that is used in half of all cancer patients. Advances in understanding the fundamentals of tumor and radiation biology, in medical physics and computer science as well as technical developments have continuously improved the effectiveness and healing success of radiotherapy. Patients benefit from new treatment concepts such as hypofractionated radiotherapy for breast and prostate cancer, leading to a reduction in the duration of treatment by several weeks. Selected patients with early stages of breast cancer can be treated with partial breast irradiation with focus on the tumor bed after breast conserving surgery increasing tolerability and comfort. High dose stereotactic radiotherapy over five to six sessions of radiation or only one fraction (radiosurgery) have expanded treatment options for common tumor entities leading to long-lasting tumor control resulting in improved survival and quality of life for those affected. In early lung cancer stereotactic radiotherapy is an alternative to primary tumor surgery. For patients with oligometastatic tumor disease stereotactic radiotherapy allows a curative approach by effectively treating metastases. In patients with brain metastases whole-brain irradiation is replaced by stereotactic irradiation of the individual metastases with fewer side effects. Recently, promising results for improved tumor control with the combination of radiotherapy and immunotherapy have been presented. Radioimmunotherapy represents a new therapy combination. However, final assessment of its efficacy and side effects profile is still missing. In order to gain therapeutic certainty, further prospective study data are necessary.

Local control and intermediate-term cosmetic outcome following IMRT for nasal tumors : An update.

OBJECTIVE: This study aims to evaluate local control and intermediate-term cosmetic outcome in patients with cancer of the nose treated with intensity-modulated radiotherapy (IMRT). METHODS: From June 2008 to September 2015, 36 consecutive patients presenting with nasal cavity, ala of the nose, or nasal vestibule tumors were treated at the Department of Radiation Oncology, University Hospital Zurich either postoperatively (n = 14; 3/14 with nasal ablation) or with definitive IMRT (n = 22). Of these 36 patients, 8 presented with recurrent disease after surgery only and 1/36 with N1 disease. Concurrent systemic therapy was administered in 18/36 patients (50%). Nasal follow-up (FU) imaging documentation of 13 patients with preserved organ and >6 months FU offers a pre/post IMRT FU comparison. In addition, these patients' subjective evaluation of cosmesis was assessed. RESULTS: Mean/median FU was 41/33 months (range 5-92 months). Salvage ablation with curative intent was undergone by 3 patients with local relapse after definitive (n = 2) and postoperative (n = 1) IMRT. The 3­year local control, ultimate local control, and overall survival rates were 90, 97, and 90 %, respectively. Subjective and objective cosmetic outcome after IMRT is very satisfying so far. CONCLUSION: IMRT for nasal tumors was found to be effective and well tolerated. Intermediate-term cosmetic results are good. Radical surgical procedures may be saved for curative salvage treatment.

Neutrophil-lymphocyte ratio complements volumetric staging as prognostic factor in patients treated with definitive radiotherapy for oropharyngeal cancer.

BACKGROUND: Volumetric tumor staging has been shown as superior prognostic tool compared to the conventional TNM system in patients undergoing definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer. Recently, clinical immunoscores such as the neutrophil-lymphocyte ratio (NLR) have been investigated as prognostic markers in several tumor entities. The aim of this study was to assess the combined prognostic value of NLR and tumor volume in patients treated with IMRT for oropharyngeal cancer (OC). METHODS: Data on all consecutive patients treated for locally advanced or inoperable OC with IMRT from 2002-2011 was prospectively collected. Tumor volume was assessed based on the total gross tumor volume (tGTV) calculated by the treatment planning system volume algorithm. The NLR was collected by a retrospective analysis of differential blood count before initiation of therapy. RESULTS: Overall, 187 eligible patients were treated with a median IMRT dose of 69.6 Gy. Three-year recurrence-free survival (RFS) for low, intermediate, high and very high tumor volume groups was 88%, 74%, 62% and 25%, respectively (p = 0.007). Patients with elevated NLR (>4.68) showed a significantly decreased 3-year RFS of 44% vs. 81% (p < 0.001) and 3-year OS of 56% vs. 84% (p < 0.001). The NLR remained a significant prognostic factor for RFS and OS when tested among tumor volume groups. Univariate and multivariate regression analysis confirmed both tumor volume and NLR as independent prognostic factors. The NLR offered further statistically significant prognostic differentiation of the small/intermediate/large tumor volume groups. CONCLUSION: The NLR remains an independent prognostic factor for patients with OC undergoing radiotherapy independent of the tumor volume.

Comparison of PET and CT radiomics for prediction of local tumor control in head and neck squamous cell carcinoma.

PURPOSE: An association between radiomic features extracted from CT and local tumor control in the head and neck squamous cell carcinoma (HNSCC) has been shown. This study investigated the value of pretreatment functional imaging (18F-FDG PET) radiomics for modeling of local tumor control. MATERIAL AND METHODS: Data from HNSCC patients (n = 121) treated with definitive radiochemotherapy were used for model training. In total, 569 radiomic features were extracted from both contrast-enhanced CT and 18F-FDG PET images in the primary tumor region. CT, PET and combined PET/CT radiomic models to assess local tumor control were trained separately. Five feature selection and three classification methods were implemented. The performance of the models was quantified using concordance index (CI) in 5-fold cross validation in the training cohort. The best models, per image modality, were compared and verified in the independent validation cohort (n = 51). The difference in CI was investigated using bootstrapping. Additionally, the observed and radiomics-based estimated probabilities of local tumor control were compared between two risk groups. RESULTS: The feature selection using principal component analysis and the classification based on the multivariabale Cox regression with backward selection of the variables resulted in the best models for all image modalities (CICT = 0.72, CIPET = 0.74, CIPET/CT = 0.77). Tumors more homogenous in CT density (decreased GLSZMsize_zone_entropy) and with a focused region of high FDG uptake (higher GLSZMSZLGE) indicated better prognosis. No significant difference in the performance of the models in the validation cohort was observed (CICT = 0.73, CIPET = 0.71, CIPET/CT = 0.73). However, the CT radiomics-based model overestimated the probability of tumor control in the poor prognostic group (predicted = 68%, observed = 56%). CONCLUSIONS: Both CT and PET radiomics showed equally good discriminative power for local tumor control modeling in HNSCC. However, CT-based predictions overestimated the local control rate in the poor prognostic validation cohort, and thus, we recommend to base the local control modeling on the 18F-FDG PET.

Risk profile for osteoradionecrosis of the mandible in the IMRT era.

BACKGROUND: The risk for osteoradionecrosis (ORN) of the mandible is positively related to bone volume exposed to > ~ 60 Gy. We hypothesized that in combined treatment, surgery may also be a risk factor. PATIENTS AND METHODS: The impact of mandibular surgery on ORN in locally disease-free IMRT cohorts was retrospectively analyzed. RESULTS: Between October 2002 and October 2013, 531 of 715 patients with oral cavity cancer (OCC), mesopharyngeal cancer (MC), or salivary gland tumor were treated with the mandible bone exposed to ~ > 60 Gy (mean follow-up, 38 months; 7-143 months). Of the 531 patients, 36 developed ORN (7 %; 1.5 % with grade 3-4). The ORN rate in definitive IMRT MC (16/227) and in postoperative IMRT OCC patients with no mandibular surgery (3/46) was 7 % each; in OCC patients with mandibular surgery the rate was 29 % (15/60, p = 0.002). Marginal or periosteal bone resection was found to be a high risk factor (39 %, vs. 7 % followed by segmental or no resection, p < 0.0001). CONCLUSION: Marginal or periosteal bone resection of the mandible was identified as the highest ORN risk factor in our IMRT cohort.

IMRT/VMAT for malignancies in the head-and-neck region : Outcome in patients aged 80.

OBJECTIVE: Elderly patients with malignant head-and-neck tumors (HNT) often pose a therapeutic challenge. They frequently have significant comorbidities which may influence their ability to tolerate tumor-specific therapies. Our aim was to investigate the outcome of patients aged 80+ years undergoing curative intent intensity- or volume-modulated radiation therapy (IMRT/VMAT). METHODS: We retrospectively reviewed our HNT patients aged 80+ treated with curative IMRT/VMAT from December 2003 to November 2015. Overall survival (OS), disease-free survival (DFS), local control (LC), and treatment tolerance were assessed. Outcome results were compared with that of a younger HNT patient cohort from our hospital. RESULTS: A total of 140 consecutive patients were included (65 postoperative, 75 definitive). Mean/median age at treatment start was 84.8/84.1 years (range 80-96 years). Mean/median follow-up time was 25/16 months (range 2-92 months). Of the 140 patients, 80 were alive with no evidence of disease when last seen, 28 had died due to the cancer, 12 remained alive with disease, the remaining 20 died intercurrently. Systemic concomitant therapy was administered in 7 %. Late grade 3-4 toxicity was observed in 2 %. All patients completed treatment. Hospitalization and feeding tube rates were 26 % and 11 %, respectively. The 2­/3-year LC, DFS, and OS rates for the entire cohort were 81/80 %, 69/63 %, and 68/66 %, respectively. Squamous cell carcinoma (SCC) patients showed an inferior 3-year OS rate as compared to non-SCC patients (62 % vs 77 %, p = 0.0002), while LC and DFS did not differ. Patients undergoing postoperative radiation attained a higher OS compared to the definitively irradiated subgroup with 74 vs. 60 % at 3 years (p = 0.01); however, DFS rates were similar for both groups (68 vs. 61 %, p = 0.15). Corresponding rates for >1400 HNT patients <80 years treated during the same time interval were 81/80 %, 69/67 %, and 77/72 %, respectively. CONCLUSIONS: Treatment tolerance in our patients aged 80+ was high. These results suggest that elderly HNT patients should not be denied potentially curative treatment strategies.

Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers : Secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10/94).

BACKGROUND: To determine the influence of baseline laboratory values on treatment outcome in patients with locally advanced head and neck cancer (HNSCC). METHODS: Data of the randomized trials ARO 95 -06 (n = 384) and SAKK 10 /94 (n = 224) were pooled for a total sample size of 608 patients. Haemoglobin (Hb) and creatinine (Cr) were available at baseline and their association with locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using univariable and multivariable Cox regression models. RESULTS: A total of 580 and 564 patients were available with baseline Hb and Cr values in the pooled analysis. Univariable analyses revealed that lower baseline Hb values were significantly associated with decreased LRRFS, DMFS, CSS and OS. This effect remained significant for OS when the treatment arms (radiotherapy [RT] alone vs. chemoradiation [CRT]) were analyzed separately. Higher baseline Cr was associated with improved OS in the pooled analysis. Interestingly, the prognostic value of baseline Cr appeared to be limited to the subgroup of 284 patients who were treated with CRT. In the multivariable Cox regression model lower baseline Hb remained associated with decreased OS both in the patients who received CRT (HR 0.79, 95 % CI 0.66-0.94, p = 0.009) and in those patients who underwent RT alone (HR 0.67, 95 % CI 0.58-0.78, p < 0.001). Increased baseline Cr remained significantly associated with improved OS in patients who underwent CRT (HR 0.79, 95 % CI 0.69-0.92, p = 0.002) but not in those patients who underwent RT alone. CONCLUSIONS: An association between lower baseline Hb and inferior treatment outcome was confirmed. Baseline Cr was introduced as a prognosticator of outcome after CRT for locally advanced HNSCC.

Less may be more: nodal treatment in neck positive head neck cancer patients.

Ongoing debates about the need and extent of planned neck dissection (PND), and required nodal radiation doses volumes lead to this evaluation. Aim was to assess nodal control after definitive intensity modulated radiation therapy (IMRT ± systemic therapy) followed by PND in our head neck cancer cohort with advanced nodal disease. Between 01/2005 and 12/2013, 99 squamous cell cancer HNC patients with pre-therapeutic nodal metastasis ≥3 cm were treated with definitive IMRT followed by PND. In addition, outcome in 103 patients with nodal relapse after IMRT and observation only (no-PND cohort) were analyzed. Prior to PND, PET-CT, fine needle aspirations, ultrasound and palpation were assessed regarding its predictive value. Patterns of nodal relapse were assessed in patients with isolated neck failure after definitive IMRT alone. 70/99 (70 %) PND specimens showed histopathological complete response (hCR), which translated into statistically significantly superior survival compared with partial response (hPR) with 4-year overall survival, disease specific survival and nodal control rates of 90/83/96 vs 67/60/78 % (p = 0.002/0.001/0.003). 1/99 patient developed isolated subsequent nodal disease. 64/2147 removed nodes contained viable tumor (3 %). Predictive information of the performed diagnostic investigations was not reliable. 17/70 hCR patients showed true negative findings in available three to four investigations (0/29 hPR). 27/103 no-PND patients developed isolated neck disease (26 %) with successful salvage in 21/24 [88 %, or 21/27 (78 %)]. Nearly all failures occurred in the prior nodal gross tumor volume area. A more restrictive approach regarding PND and/or nodal IMRT dose-volumes may be justified.

Combined PET/CT-perfusion in patients with head and neck cancers might predict failure after radio-chemotherapy: a proof of concept study.

BACKGROUND: [18F]FDG-PET/CT imaging is broadly used in head and neck cancer (HNSCC) patients. CT perfusion (CTP) is known to provide information about angiogenesis and blood-flow characteristics in tumors. The aim of this study was to evaluate the potential relationship of FDG-parameters and CTP-parameters in HNSCC preand post-therapy and the potential prognostic value of a combined PET/CT with CTP. METHODS: Thirteen patients with histologic proven HNSCC were prospectively included. All patients underwent a combined PET/CT with integrated CTP before and after therapy. Pre- and post-therapeutic data of CTP and PET of the tumors were compared. Differences were tested using Spearman's rho test and Pearson's correlation. A p-value of p <0.05 was considered statistically significant. Correlations were calculated using Pearson's correlation. Bootstrap confidence intervals were calculated to test for additive confidence intervals. RESULTS: Three patients died due to malignancy recurrence, ten patients were free of recurrence until the end of the follow-up period. Patients with recurrent disease had significantly higher initial CTP-values compared to the recurrence-free patients: BFpre 267.4 (171.2)ml/100 mg/min, BVpre 40.9 (8.4)ml/100 mg and MTTpre 8.2 (6.1)sec. No higher SUVs initially but significantly higher TLG compared to patients without recurrence were found. Post-therapeutic PET-values differed significantly between the two groups: SUVmaxpost 6.0 (3.2), SUVmeanpost 3.6 (2.0) and TLG 21751.7 (29794.0). CONCLUSION: In our proof of concept study, combined PET/CT with integrated CTP might show complementary prognostic data pre- and post chemo-radiotherapy. CTP may be used to predict local tumor recurrence, while FDGPET/CT is still needed for whole-body staging.

Carotid artery disease after head and neck radiotherapy.

Radiation induced atherosclerosis of the carotid artery is a clinically relevant late complication after head and neck radiotherapy. Improved long-term survival after multimodality therapy in neck malignancies result in an increased risk of carotid artery disease in patients after radiotherapy (RT). This review focuses on the current knowledge of occlusive carotid disease after head and neck radiotherapy and highlights the exceeding morphologic post-radiation vessel wall pathologies. More severe and extensive carotid artery atherosclerosis with plaque in all segments including the common carotid artery is a frequent finding after RT. Therefore, colour coded duplex ultrasound surveillance in patients after head and neck RT is recommended. Some histopathological studies indicate differences to “classical” atherosclerosis, and pathogenesis of chronic radiation vasculopathy is still under discussion.

Time-Related Outcome Following Palliative Spatially Fractionated Stereotactic Radiation Therapy (Lattice) of Large Tumors - A Case Series.

Purpose: Lattice radiation therapy (LRT), a form of spatially fractionated radiation therapy, holds promise for treating large tumors. Despite its introduction in clinical practice around 2010, there remains limited information on its time-related outcomes despite consistently high response rates and tolerability. We assessed the time-related outcome of our palliative LRT cohort. Methods and Materials: We conducted an analysis of our LRT program, which involved 45 palliative patients with 56 lesions larger than 7 cm, treated between January 2022 and November 2023. Prospectively defined treatment protocols included delivering 20 to 25 Gy/5 fractions to the tumor with a stereotactic simultaneously integrated boost (SIB) of 60 to 65 Gy to lattice vertices (n = 45/56) or, mainly in preirradiated lesions, single fraction stereotaxy with 1 × 15 to 20 Gy to vertices only (n = 11/56). Follow-up (FU) intervals were determined based on clinical considerations, considering the mostly highly palliative situation of included patients. Outcome assessments focused on subjective benefit and objective radiologic FU response. Results: The mean/median FU was 5.5/4.0 months (0.3-21 months). A total of 25/45 (56%) patients died after a mean/median of 3.9/2.0 months (0.3-14 months). Fourteen of 56 lesions (25%) were previously irradiated, with a mean/median of 18/13 months (4-72 months) prior to LRT. The mean/median gross tumor volume (GTV) measured 797/415 cc (54-4027 cc) and 14/13 cm (7-28 cm). Subjective statements at LRT completion were available from 37 symptomatic patients: 32/37 (87%) reported fast symptom relief, and 5/37 felt no change under LRT or at LRT completion. Early tolerance was excellent (G0-1). FU imaging was available from 40/56 lesions (71%): progression in 3/40 at first exam one at 1.5 and 4 months post-LRT, and stable disease (±10%) in 5/40 assessed at 2, 3, 3, and 4 months post-LRT. First measure shrinkage of 48%/30% (10%-100%) was found in 32/40 lesions (80%) after a mean/median of 2.8/3 months (0.3-7 months). Maximum shrinkage over time based on 21 cases with at least 1 FU imaging measured a mean/median of 62%/60% after 6.2/5.5 months. The duration of radiologic response was a mean/median of 7.4/7.0 months (1-21 months). Conclusions: Short-course LRT emerged as an effective and well-tolerated palliative option for very large lesions, whether treatment-naïve or previously irradiated. Nearly 90% of symptomatic patients reported significant subjective benefit, and 80% of assessed lesions demonstrated tumor shrinkage ≥10%, with a mean response duration of >6 months.

Preoperative Ultrahypofractionated Radiation Therapy for Soft Tissue Sarcomas: Low Rate of Wound Complications.

Purpose: Normofractionated preoperative radiation therapy (nRT) with 50 Gy applied in 25 fractions represents the most widely used radiation therapy (RT) regimen in combined local treatment of soft tissue sarcomas (STSs). STSs are characterized by a low α/ß ratio of 4 to 5 Gy, which may translate into a higher sensitivity for hypofractionation. Increasing data from cohorts and phase 2 trials on ultrahypofractionated RT (uhRT) regimens are available. We prospectively assessed our preoperative uhRT sarcoma patient cohort with a focus on short-term wound complications (WCs). Methods and Materials: This is a prospective registry analysis of a single-center patient cohort, treated from 03.2020 to 10.2023 with uhRT (25 Gy in 5 fractions in 1 week). The same radiation oncologists (G.S./C.G.) and surgeon (B.F.) performed the treatment (61/61 and 58/60), as well as the same reference pathologist (B.B.) confirmed all histopathologic diagnoses. WC (according to CAN-NCIC-SR2 trial) and intermediate local control (LC) rates were assessed and compared with outcome data of a previously published cohort of 67 extremity/trunk sarcoma patients treated with nRT by the same authors (7% WC, 98% LC at 3 years). Results: After a mean/median follow-up of 19/19 months (range, 0-46), LC at 1.5 years was 94%. Surgery was performed at a mean/median of 20/16 days (range, 4-60) after uhRT completion. WC were observed in 7/60 operated patients (12%), and in 5/51 (10%) extremity/trunk lesions. Early tolerance was excellent, limited to G0 to G1, even in 3 patients with prior RT to the same region. Clear resection margins were achieved in 55/60 patients (92%). Pathologic necrosis of ≥95% was reported in 5% and 75% achieved less than 50% necrosis. Conclusions: These results show low rates of WC and high LC for uhRT and are comparable with our previously published nRT data. This study supports the routine use of preoperative uhRT for STS.

Real-World-Time Data and RCT Synergy: Advancing Personalized Medicine and Sarcoma Care through Digital Innovation.

This manuscript examines the synergistic potential of prospective real-world/time data/evidence (RWTD/E) and randomized controlled trials (RCTs) to enrich healthcare research and operational insights, with a particular focus on its impact within the sarcoma field. Through exploring RWTD/E's capability to provide real-world/time, granular patient data, it offers an enriched perspective on healthcare outcomes and delivery, notably in the complex arena of sarcoma care. Highlighting the complementarity between RWTD/E's expansive real-world/time scope and the structured environment of RCTs, this paper showcases their combined strength, which can help to foster advancements in personalized medicine and population health management, exemplified through the lens of sarcoma treatment. The manuscript further outlines methodological innovations such as target trial emulation and their significance in enhancing the precision and applicability of RWTD/E, underscoring the transformative potential of these advancements in sarcoma care and beyond. By advocating for the strategic incorporation of prospective RWTD/E into healthcare frameworks, it aims to create an evidence-driven ecosystem that significantly improves patient outcomes and healthcare efficiency, with sarcoma care serving as a pivotal domain for these developments.

Impact of Institutional Practices and Surgical Complexity on Sarcoma Surgery Costs: Driving Efficiency in Value-Based Healthcare.

BACKGROUND: Sarcomas present a unique challenge within healthcare systems due to their rarity and complex treatment requirements. This study explores the economic impact of sarcoma surgeries across three Swiss tertiary healthcare institutions, utilizing a consistent surgical approach by a single surgeon to eliminate variability in surgical expertise as a confounding factor. METHODS: By analyzing data from 356 surgeries recorded in a real-world-time data warehouse, this study assesses surgical and hospital costs relative to institutional characteristics and surgical complexity. RESULTS: Our findings reveal significant cost variations driven more by institutional resource management and pricing strategies than by surgical techniques. Surgical and total hospitalization costs were analyzed in relation to tumor dignity and complexity scores, showing that higher complexity and malignancy significantly increase costs. Interestingly, it was found that surgical costs accounted for only one-third of the total hospitalization costs, highlighting the substantial impact of non-surgical factors on the overall cost of care. CONCLUSIONS: The study underscores the need for standardized cost assessment practices and highlights the potential of predictive models in enhancing resource allocation and surgical planning. By advocating for value-based healthcare models and standardized treatment guidelines, this research contributes to more equitable and sustainable healthcare delivery for sarcoma patients. These insights affirm the necessity of including a full spectrum of care costs in value-based models to truly optimize healthcare delivery. These insights prompt a reevaluation of current policies and encourage further research across diverse geographical settings to refine cost management strategies in sarcoma treatment.

Improving Sarcoma Outcomes: Target Trial Emulation to Compare the Impact of Unplanned and Planned Resections on the Outcome.

This study follows the Target Trial Emulation (TTE) framework to assess the impact of unplanned resections (UEs) and planned resections (PEs) of sarcomas on local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Sarcomas, malignant tumors with mesenchymal differentiation, present a significant clinical challenge due to their rarity, complexity, and the frequent occurrence of UEs, which complicates effective management. Our analysis utilized real-world-time data from the Swiss Sarcoma Network, encompassing 429 patients, to compare the impact of UEs and PEs, adjusting for known prognostic factors through a multivariable Cox regression model and propensity score weighting. Our findings reveal a significantly higher risk of local recurrence for UEs and a short-term follow-up period that showed no marked differences in MFS, CSS, and OS between the UE and PE groups, underlining the importance of optimal initial surgical management. Furthermore, tumor grade was validated as a critical prognostic factor, influencing outcomes irrespective of surgical strategy. This study illuminates the need for improved referral systems to specialized sarcoma networks to prevent UEs and advocates for the integration of TTE in sarcoma research to enhance clinical guidelines and decision-making in sarcoma care. Future research should focus on the prospective validations of these findings and the exploration of integrated care models to reduce the incidence of UEs and improve patient outcomes.

The Next Frontier in Sarcoma Care: Digital Health, AI, and the Quest for Precision Medicine.

The landscape of sarcoma care is on the cusp of a transformative era, spurred by the convergence of digital health and artificial intelligence (AI). This perspectives article explores the multifaceted opportunities and challenges in leveraging these technologies for value-based, precision sarcoma care. We delineate the current state-of-the-art methodologies and technologies in sarcoma care and outline their practical implications for healthcare providers, administrators, and policymakers. The article also addresses the limitations of AI and digital health platforms, emphasizing the need for high-quality data and ethical considerations. We delineate the promise held by the synergy of digital health platforms and AI algorithms in enhancing data-driven decision-making, outcome analytics, and personalized treatment planning. The concept of a sarcoma digital twin serves as an illustrative paradigm for this integration, offering a comprehensive, patient-centric view of the healthcare journey. The paper concludes with proposals for future research aimed at advancing the field, including the need for randomized controlled trials or target trial emulations and studies focusing on ethical and economic aspects. While the road to this transformative care is laden with ethical, regulatory, and practical challenges, we believe that the potential benefits far outweigh the obstacles. We conclude with a call to action for multidisciplinary collaboration and systemic adoption of these technologies, underscoring the urgency to act now for the future betterment of sarcoma care and healthcare at large.

Benchmarking Time-to-Treatment Initiation in Sarcoma Care Using Real-World-Time Data.

Benchmarking is a fundamental tool for enhancing quality within a patient-centered healthcare framework. This study presents an analysis of time-to-treatment initiation (TTI) for sarcoma patients, utilizing a database encompassing 266 cases from the Swiss Sarcoma Network. Our findings indicate a median TTI of 30 days across the cohort, with bone sarcomas and deep soft tissue sarcomas demonstrating a shorter median TTI of 28 days, followed by superficial soft tissue sarcomas at 42 days. The data reveal that the use of real-world-time data (RWTD) may account for a longer TTI observed, as it offers more comprehensive capture of patient journeys, unlike conventional datasets. Notably, variability in TTI was observed between different treatment institutions, which underscores the need for standardized processes across centers. We advocate for a selective referral system to specialized centers to prevent capacity overload and ensure timely treatment initiation. Our analysis also identified significant delays in TTI for unplanned 'whoops'-resections, highlighting the importance of early specialist referral in optimizing treatment timelines. This study emphasizes the potential benefits of a streamlined, data-informed approach to sarcoma care. However, further research is required to establish the direct impact of integrated care models on TTI and patient outcomes in the context of sarcoma treatment.

Enhancing Healthcare for Sarcoma Patients: Lessons from a Diagnostic Pathway Efficiency Analysis.

Sarcomas, rare and with lower survival rates than common tumors, offer insights into healthcare efficiency via the analysis of the total interval of the diagnostic pathway, combining the patient interval (time between the first symptom and visit with a physician) and diagnostic interval (time between first physician visit and histological diagnosis). Switzerland's healthcare system, Europe's costliest, lacks research on treating rare conditions, like mesenchymal tumors. This study examines the total interval of the diagnostic pathway for optimization strategies. Analyzing a dataset of 1028 patients presented from 2018 to 2021 to the Swiss Sarcoma Board (MDT/SB-SSN), this retrospective analysis delves into bone sarcoma (BS), soft-tissue sarcoma (STS), and their benign counterparts. Demographic and treatment data were extracted from medical records. The patient interval accounted for the largest proportion of the total interval and secondary care interval for the largest proportion of the diagnostic interval. Age, grade, and localization could be elicited as influencing factors of the length of different components of the total interval. An increasing age and tumor size, as well as the axial localization, could be elicited as factors increasing the probability of sarcoma. The patient and secondary care interval (SCI) offer the greatest potential for optimization, with SCI being the bottleneck of the diagnostic interval. New organizational structures for care work-ups are needed, such as integrated practice units (IPU) as integral part of value-based healthcare (VBHC).

Early and Intermediate Treatment Outcome After Postoperative External Beam Accelerated Partial Breast Irradiation in Patients With Early-Stage Breast Cancer.

PURPOSE: To prospectively evaluate early and intermediate outcome after accelerated partial breast irradiation (APBI) in patients early-with stage breast cancer. METHODS AND MATERIALS: Inclusion criteria were defined according to the APBI American Society for Radiation Oncology's ASTRO Evidence-Based Consensus Statement. The prescribed dose was 26 to 28 Gy in 5 fractions on 5 consecutive days. Regular follow-up visits with objective and subjective evaluation of treatment tolerance were performed after 0 and 2 weeks, 6 months, and at annual intervals. RESULTS: Between February 2017 and January 2020, 175 patients with breast conserving surgery met the inclusion criteria for APBI. Mean age was 65.7 years (range, 46-88). Thirteen percent of patients received a diagnosis with carcinoma in situ, 55%, 35%, and 37% with T1a/b/c, and 10% with T2 stages, respectively. The mean volume of planning target volume (PTV) was 119 cc (range, 45-465), the ratio of mean PTV: whole breast volume ratio was 21% (7%-53%). Mean follow-up was 42 months (median, 45, range, 0-67). Acute toxicity after 2 weeks was low with 69%, 26%, and 5% grade 0, 1, and 2. In addition, 1-, 2-, 3-, 4-, and 5-year follow-up data were available from 146, 134, 107, 73, and 25 patients. Patient-reported cosmetic outcomes were assessed excellent or good in 97.9%, 98.5%, 98.1%, 98.6%, and 100%. Regarding grade 2 toxicities, as by now 3%, 2%, 2%, 0%, and 0% G2 fibrosis, 1%, 1%, 0%, 0%, and 0% G2 atrophy, no G2 skin telangiectasia or breast edema occurred. So far, none of the patients have experienced G3 toxicity or higher. The remaining patients had grade 0 or 1 toxicity only. Five ipsilateral breast recurrences (1 marginally to PTV, 4 out-of-field) and 5 distant recurrences were recorded by March 2023. The 4-year in-breast recurrence rate was 2.5%. Eight patients died, with 2 of them from disease. For all patients, the 4-year overall, cancer specific and disease-free survival rates were 97.1%, 99.4%, and 95.3%, respectively. CONCLUSIONS: We showed high early- and intermediate-term treatment tolerance and disease control of APBI using 26 to 28 Gy in five fractions in one week in carefully selected patients with early breast cancer. APBI is highly appreciated by patients and efficient, as an additional advantage for busy centers.