Radiotherapy is intriguing as it not only eliminates tumor cells but also triggers a response from cytotoxic T cells, which attack the tumor. Thus, radiotherapy and immunotherapy are being combined... Show moreRadiotherapy is intriguing as it not only eliminates tumor cells but also triggers a response from cytotoxic T cells, which attack the tumor. Thus, radiotherapy and immunotherapy are being combined in clinical studies, although their success has been limited. We used mouse tumor models to understand how radiotherapy induces T cell priming and subsequent anti-tumor immunity. In a model resembling lymphocyte-depleted cancer, we identified obstacles to systemic radiotherapy-induced T cell responses and proposed interventions to overcome them. Additionally, we explored strategies to counter local T cell suppression in the tumor microenvironment. In poorly immunogenic tumors, radiotherapy can provoke a T cell response, but this is counteracted by the generation of immunosuppressive Tregs. Combining radiotherapy with checkpoint immunotherapy, despite its success in humans, unexpectedly amplified the Treg response, further hindering cytotoxic T-cell activity. Our findings suggest this immunotherapy may not benefit these cancers. We discovered that molecules like CD80 and CD86, capable of stimulating T cells via the CD28 receptor, have distinct roles in promoting cytotoxic and Treg cells. Blocking CD86 enhanced cytotoxic T cell responses post-radiotherapy, leading to tumor rejection. Our study elucidates how tumor characteristics shape T-cell responses, how radiotherapy can evoke both favorable and unfavorable responses, and how targeted antibody immunotherapy can influence this interplay. Show less
Bosch, S. van den; Takes, R.P.; Ridder, M. de; Bree, R. de; Al-Mamgani, A.; Schreuder, W.H.; ... ; Kaanders, J.H.A.M. 2024
BackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable... Show moreBackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life.Methods/designThis is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment.DiscussionIf this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care. Show less
This thesis focuses on treatment outcomes of high risk endometrial cancer and corresponding patients’ and clinicians’ preferences regarding adjuvant treatment decisions; molecular studies on the... Show moreThis thesis focuses on treatment outcomes of high risk endometrial cancer and corresponding patients’ and clinicians’ preferences regarding adjuvant treatment decisions; molecular studies on the etiology of mismatch repair deficiency (MMRd) in intermediate and high risk endometrial cancer; and the combination of immunotherapy and PARP inhibition for the treatment of recurrent or metastatic endometrial cancer.The overall aims of this thesis were:• To evaluate health-related quality of life up to 5 years after chemoradiotherapy compared with pelvic radiotherapy alone in the adjuvant treatment of high risk endometrial cancer in the PORTEC-3 trial;• To investigate the preferences of patients and clinicians regarding the benefit-risk trade-off of the addition of chemotherapy to adjuvant pelvic radiotherapy;• To investigate the prevalence and prognosis of Lynch syndrome-associated endometrial cancer among MMRd endometrial cancers;• To evaluate the role of combined checkpoint inhibition and PARP inhibition in women with metastatic or recurrent endometrial cancer in terms of progression-free survival and toxicity in the DOMEC trial. Show less
For part I population-based data from the national cancer registries of Belgium, the Netherlands, Norway, and Sweden was used. In all countries, the use of chemotherapy increased with stage and... Show moreFor part I population-based data from the national cancer registries of Belgium, the Netherlands, Norway, and Sweden was used. In all countries, the use of chemotherapy increased with stage and decreased with age. Also, 30-day and one-year excess mortality decreased over the years for colon and rectal cancer. After surviving the first postoperative year, the survival of surgically treated older patients aligned with their younger counterparts, except for patients with stage III disease. Part II describes the results of the analyses of the RAPIDO trial. DRTF decreased from 30% in the standard-care group to 24% in the experimental group at 3 years after randomisation, mainly due to a decrease in DM, which is probably due to better compliance preoperatively and perhaps due the earlier treatment of micrometastases in the treatment process. Although patients with DM in the experimental group had worse survival compared to patients in the standard-care group, the cumulative probability of overall survival remained comparable for both treatment groups. If the patients with a complete response can be identified during reassessment after neoadjuvant therapy, surgery may be omitted, a W&W after a cCR with an appropriate follow-up has no additional oncological risk in young patients compared to older patients (part III). This opens the door for potential organ preservation. Show less
Objective: To analyze the effect of dizziness-related symptoms on the long-term quality of life (QoL) of patients with unilateral vestibular schwannoma. Methods: In this cross-sectional study,... Show moreObjective: To analyze the effect of dizziness-related symptoms on the long-term quality of life (QoL) of patients with unilateral vestibular schwannoma. Methods: In this cross-sectional study, patients with a unilateral vestibular schwannoma diagnosed between 2004 and 2013 completed a disease-specific QoL questionnaire (Penn Acoustic Neuroma Quality of Life [PANQOL]) and the Dizziness Handicap Inventory (DHI) in 2020. Linear regression was performed to assess the correlation between QoL and the DHI total score, and the scores of the DHI functional, emotional, and physical subdomains. Potential confounders such as age, sex, tumor size at baseline, and treatment modality (active surveillance, surgery, or radiotherapy) were included in the model. Results: In total, 287 of 479 patients (59%) experienced dizziness with a median follow-up of 10 years. The DHI total score was significantly associated with the PANQOL total score. On average, we found a reduction of 0.7 points on the PANQOL for each additional point on the DHI. The DHI emotional subdomain was the most prominent determinant of poorer QoL. Each point on the DHI emotional subscale was associated with a reduction of 1.3 on the PANQOL score. Treatment modality did not have a clinically relevant effect on dizziness-related QoL. Conclusions: Even mild dizziness can have a significant and clinically relevant effect on the QoL of patients with unilateral vestibular schwannoma in the long term. This holds true for all treatment modalities. Addressing the vestibular problems may improve QoL in vestibular schwannoma patients, and DHI subscale analysis may help tailor the optimal vestibular intervention. Show less
Objective: In vestibular schwannoma patients, a loss of signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) has been reported within the ipsilateral labyrinth. The purpose of this... Show moreObjective: In vestibular schwannoma patients, a loss of signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) has been reported within the ipsilateral labyrinth. The purpose of this study was to quantitatively evaluate the occurrence and course of this intensity loss in relation to proton radiotherapy and its possible association with hearing loss. Study Design: Retrospective chart review. Setting: Tertiary referral center. Patients: Patients who received proton therapy for a vestibular schwannoma and underwent at least two high-resolution T2-weighted cisternographic sequence (constructive interference in steady state/fast imaging employing steady-state acquisition/DRIVE) MRIs and audiometry assessments. Main Outcome Measures: Relative T2 SIs from the vestibules and basal/apical cochlear turns of the labyrinth, bilaterally.ResultsNinety-five MRI scans from 34 patients were included. The apical turn of the ipsilateral cochlea showed a lower mean cochlear SI than on the contralateral side (+/- 3.5 versus 5.0). The mean relative cochlear SI did not significantly change after proton radiotherapy. The ipsilateral vestibule showed a higher SI than the cochlea. The relative mean cochlear SI was not directly correlated to (the degree of) hearing loss before or after proton radiotherapy, nor did it predict future hearing loss. Conclusion: The relative mean cochlear SI on cisternographic T2-MRI in vestibular schwannoma patients is diminished on the treated side, when compared with the ipsilateral vestibule and the contralateral cochlea/vestibule. The SI of the ipsilateral cochlea does not further decrease after proton radiotherapy and seems to be related to the tumor rather than the therapy. The diminished cochlear SI does not correlate with subsequent loss of hearing. Show less
Kolk, W.L. van der; Zee, A.G.J. van der; Slomovitz, B.M.; Baldwin, P.J.W.; Doorn, H.C. van; Hullu, J.A. de; ... ; GROINSS-V I II Participants 2022
Objective. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear.... Show moreObjective. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN.Methods. We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up.Results. Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was di-agnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor >= 30 mm. Bilateral ra-diotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence.Conclusion. The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Ghuijs, W.; Kemps, P.G.; Capala, M.E.; Verdijk, R.M.; Halteren, A.G.S. van; Wal, R.J.P. van der; Laar, J.A.M. van 2022
Background Langerhans cell histiocytosis (LCH) is a rare haematological neoplasm characterized by the accumulation of CD1a(+), CD207/Langerin(+) histiocytes within inflammatory lesions. LCH can... Show moreBackground Langerhans cell histiocytosis (LCH) is a rare haematological neoplasm characterized by the accumulation of CD1a(+), CD207/Langerin(+) histiocytes within inflammatory lesions. LCH can involve any organ, but osteolytic bone lesions are most often encountered. Unifocal bone lesions may regress spontaneously after a thick needle biopsy has been taken. Case presentation In this case report, we describe the initial presentation of a single BRAF(V600E) mutated osteolytic LCH lesion in the left proximal humerus of a 46-year-old previously healthy woman. Despite multiple surgical interventions, she unexpectedly experienced progressive disease manifestation with significant soft tissue extension to the surrounding musculature, subcutis and epidermis. Because the disease manifestation remained loco-regional, radiotherapy (RT) (total dose of 20 Gy in 10 fractions) was initiated. Conclusion The patient achieved a complete remission without any side effects. This case highlights that RT is a rational and relative mild local treatment option for patients with aggressive LCH affecting the bone and surrounding soft tissue. Show less
Hendriksma, M.; Heijnen, B.J.; Verbist, B.M.; Jong, M.A. de; Langeveld, A.P.M.; Benthem, P.P.G. van; Sjogren, E.V. 2022
Objective: To evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour-node stage T2N0 glottic carcinoma, stratified for tumour extension. Methods: A... Show moreObjective: To evaluate the long-term functional outcomes in patients who received primary radiotherapy for tumour-node stage T2N0 glottic carcinoma, stratified for tumour extension. Methods: A cross-sectional study was performed on patients who were treated with radiotherapy for T2N0 glottic carcinoma. Four questionnaires were used to measure different aspects of functional outcome. In addition, objective evaluation and perceptual analysis were performed. Results: Fourteen patients were included in this study. The median time between the start of radiotherapy and assessment was 42 months (range, 26-143 months). Patients reported high-level functioning, with low symptom scores and good swallowing function, and showed a median dysphonia grade of 1.5. The median Voice Handicap Index-30 score was 17.5. Conclusion: Patients with T2N0 glottic carcinoma treated with radiotherapy had good long-term quality of life, with low symptom scores, good swallowing functioning and slightly elevated voice outcome parameters. Show less
Acem, I.; Schultze, B.T.A.; Schoonbeek, A.; Houdt, W.J. van; Sande, M.A.J. van de; Visser, J.J.; ... ; Verhoef, C. 2022
Introduction: There is no clear evidence regarding the benefit of restaging for distant metastases after neoadjuvant radiotherapy (RTX) in patients with soft tissue sarcoma (STS) of the extremities... Show moreIntroduction: There is no clear evidence regarding the benefit of restaging for distant metastases after neoadjuvant radiotherapy (RTX) in patients with soft tissue sarcoma (STS) of the extremities and trunk wall. This study aimed to determine how often restaging of the chest identified metastatic disease that altered management in these patients.Methods: We performed a single-centre retrospective study from 2010 to 2020. All patients with non-metastatic STS of the extremities and trunk wall who were treated with neoadjuvant RTX and received a staging and restaging chest CT scan or X-ray for distant metastasis were included. The outcome of interest was change in treatment strategy due to restaging after neoadjuvant RTX.Results: Within the 144 patients who were staged and treated with neoadjuvant RTX, a restaging chest CT or X-ray was performed in 134 patients (93%). A change in treatment strategy due to new findings at restaging after RTX was observed in 26 out of 134 patients (19%). In 24 patients the scheduled resection of the primary STS was cancelled at restaging (24/134, 18%), given the findings at restaging. The other two patients did receive the intended local resection, but either with palliative intent, or as a part of a previously unplanned multimodality treatment.Conclusion: In approximately one in five patients restaging results in a change in treatment strategy. This underlines the added value of routine restaging for distant metastases with chest CT or X-ray after neoadjuvant RTX in patients with STS. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Introduction: This subgroup analysis of undifferentiated pleomorphic soft tissue sarcoma of the extremity (eUPS) from the PERSARC collaborative group aimed to achieve a more personalized... Show moreIntroduction: This subgroup analysis of undifferentiated pleomorphic soft tissue sarcoma of the extremity (eUPS) from the PERSARC collaborative group aimed to achieve a more personalized multimodality treatment approach for primary eUPS in elderly patients. Material and methods: A multicenter retrospective study including primary high-grade eUPS surgically treated with curative intent between 2000 and 2016. Overall survival (OS), local recurrence (LR) and distant metastasis (DM) curves were calculated by Kaplan Meier analysis. Cox proportional hazard models were used to determine the effect of radiotherapy. Results: From a total of 2511 patients with extremity soft tissue sarcoma (eSTS) of the PERSARC study collaborative; 703 patients with eUPS were included in this study. In elderly patients with eUPS 5-year OS, LR and DM were 35.4 (95%CI 29.3-42.8), 17.7 (95%CI 12.7-22.6) and 24.6 (95%CI 19.1-30.1). eUPS was significantly less treated with radiotherapy compared with other eSTS, especially in elderly patients. Patients with R1-R2 margins treated with radiotherapy had about half the risk of developing LR compared with patients treated without radiotherapy (HR = 0.454, p = 0.033). Conclusion: Elderly patients with eUPS were less often treated with radiotherapy and showed higher LR. Nowadays, given an increasing life expectancy in elderly patients, multimodality treatment should be considered. (C) 2021 The Authors. Published by Elsevier Ltd. Show less
Olthof, E.P.; Wenzel, H.; Velden, J. van der; Spijkerboer, A.M.; Bekkers, R.; Beltman, J.J.; ... ; Mom, C. 2022
Objective Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical... Show moreObjective Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment. Methods Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes >= 1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis. Results Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83). Conclusions This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors. Show less
During recent decades, many studies have been performed in patients with early glottic cancer, which provide new insight into the two main treatment modalities, TOLMS and radiotherapy, and their... Show moreDuring recent decades, many studies have been performed in patients with early glottic cancer, which provide new insight into the two main treatment modalities, TOLMS and radiotherapy, and their outcomes. The aim of this thesis was: (i) What is the role of TOLMS in T2 glottic carcinoma in the Netherlands? (ii) Should more patients with T2 glottic carcinoma be treated with TOLMS? Within this thesis, we found that (i) the laryngeal preservation rate for T2 glottic carcinoma is higher after primary treatment with TOLMS than after primary treatment with radiotherapy; (ii) that the binary use (yes/no) for the involvement of the anterior commissure (AC) as a prognostic factor leads to inconsistent results, whereas studies with a more detailed classification of the AC show that there is a significant impact on oncological outcomes; (iii) that vertical involvement of the AC on imaging has a significant impact on local control not only in patients treated with TOLMS but also in patients receiving primary radiotherapy; and (iv) that patient with T2 glottic carcinoma treated with radiotherapy reported good long-term functional outcomes, although patients with tumors infiltrating the vocal fold muscle show a trend toward a higher degree of voice handicap than patients with tumor with only superficial spread. Show less
Background Radiotherapy (RT) is part of the curative treatment of approximately 70% of breast cancer (BC) patients. Wide practice variation has been reported in RT dose, fractionation and its... Show moreBackground Radiotherapy (RT) is part of the curative treatment of approximately 70% of breast cancer (BC) patients. Wide practice variation has been reported in RT dose, fractionation and its treatment planning for BC. To decrease this practice variation, it is essential to first gain insight into the current variation in RT treatment between institutes. This paper describes the development of the NABON Breast Cancer Audit-Radiotherapy (NBCA-R), a structural nationwide registry of BC RT data of all BC patients treated with at least surgery and RT. Methods A working group consisting of representatives of the BC Platform of the Dutch Radiotherapy Society selected a set of dose volume parameters deemed to be surrogate outcome parameters, both for tumour control and toxicity. Two pilot studies were carried out in six RT institutes. In the first pilot study, data were manually entered into a secured web-based system. In the second pilot study, an automatic Digital Imaging and Communications in Medicine (DICOM) RT upload module was created and tested. Results The NBCA-R dataset was created by selecting RT parameters describing given dose, target volumes, coverage and homogeneity, and dose to organs at risk (OAR). Entering the data was made mandatory for all Dutch RT departments. In the first pilot study (N = 1093), quite some variation was already detected. Application of partial breast irradiation varied from 0 to 17% between the 6 institutes and boost to the tumour bed from 26.5 to 70.2%. For patients treated to the left breast or chest wall only, the average mean heart dose (MHD) varied from 0.80 to 1.82 Gy; for patients treated to the breast/chest wall only, the average mean lung dose (MLD) varied from 2.06 to 3.3 Gy. In the second pilot study 6 departments implemented the DICOM-RT upload module in daily practice. Anonymised data will be available for researchers via a FAIR (Findable, Accessible, Interoperable, Reusable) framework. Conclusions We have developed a set of RT parameters and implemented registration for all Dutch BC patients. With the use of an automated upload module registration burden will be minimized. Based on the data in the NBCA-R analyses of the practice variation will be done, with the ultimate aim to improve quality of BC RT. Trial registration Retrospectively registered. Show less
Adapting a radiotherapy treatment plan to the daily anatomy is a crucial task to ensure adequate irradiation of the target without unnecessary exposure of healthy tissue.This adaptation can be... Show moreAdapting a radiotherapy treatment plan to the daily anatomy is a crucial task to ensure adequate irradiation of the target without unnecessary exposure of healthy tissue.This adaptation can be performed by automatically generating contours of the daily anatomy together with fast re-optimization of the treatment plan. These measurescan compensate for the daily variation and ensure the delivery of the prescribed dose distribution at small margins and high robustness settings. In this thesis, we focused on developing a deep learning-based methodology for automatic contouring for real-time adaptive radiotherapy either guided by CT or MR imaging modalities Show less
Introduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for... Show moreIntroduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for many tumor types. These patients are increasingly referred for radiotherapy, but it is unclear whether radiotherapy combined with these drugs is safe. No international guidelines exist on whether or how to combine these drugs with radiotherapy. Therefore, we investigated the current clinical practice in the Netherlands regarding hypofractionated radiotherapy in patients using targeted drugs and immunotherapy.Materials and methods: We sent a survey to all 21 Dutch radiotherapy institutes. Dedicated radiation oncologists, medical oncologists and pulmonologists were asked to fill out the survey. The questions explored their familiarity with the combination of targeted drugs and immunotherapy with radiotherapy, the encountered clinical difficulties and factors influencing treatment decisions.Results: The survey was filled out by 54 respondents from 19 different institutes. The median annual number of patients per radiation oncologist referred for radiotherapy when using targeted drugs or immunotherapy was 10 and 15, respectively. Despite this high number, only 11% of the radiation oncologists stated that they had sufficient information (resources) for adequate treatment decision making. Among all physicians, 44% stated that there was insufficient knowledge within their institute regarding this topic. Only 17% stated that there was a multidisciplinary protocol available. The application of radiotherapy treatment adaptations (technique, dose, fractionation, field size) varied widely. Generally, there seemed to be no consensus regarding the expected toxicity of combined drug-radiotherapy treatments and the expected risk of tumor flare upon temporary drug discontinuation.Conclusion: There is no consensus amongst involved medical specialties on expected toxicity. Consequently, it is necessary to perform clinical studies examining the safety of combined drug-radiotherapy treatments, to add radiotherapy to phase I-III clinical trials for new drugs and to incorporate outcomes into multidisciplinary, evidence-based guidelines. Show less
Purpose: Total skin electron beam therapy (TSEBT) is used mostly in the treatment of cutaneous T cell lymphoma. In this study we describe the results of TSEBT applied in the Netherlands using two... Show morePurpose: Total skin electron beam therapy (TSEBT) is used mostly in the treatment of cutaneous T cell lymphoma. In this study we describe the results of TSEBT applied in the Netherlands using two different schedules, a conventional dose schedule of 35 Gy and a low-dose schedule of 12 Gy. We aimed to evaluate the treatment results in and compare treatment outcomes between the two treatment groups and to further define indications for both doses.Methods: In the LUMC, Leiden, we performed a retrospective analysis of 51 patients treated with TSEBT between January 2008 and December 2018, with follow-up untill December 2019. Thirty one patients were treated with 35 Gy and twenty with 12 Gy. The dose was chosen based on the severity of skin involvement. Outcome measures were time to meaningful progression, survival, response rate and toxicity.Results: Time to meaningful progression was 5.1 months with no significant differences between dose groups (P = 0.77). Overall survival was 27.4 months. Both time to progression and survival were significantly better for T2 vs T3 stage. Overall response rate was 80.4 %. Both dose groups showed improvement of symptoms. Treatment was generally well tolerated.Conclusions: Both high-dose and low-dose TSEBT offer similar results for TMP and OS. It remains unclear which patients benefit most from a high-dose schedule. We propose to use the low-dose schedule as a standard for TSEBT and use supplementary boosts or escalation to high-dose treatment for patients unresponsive to the low-dose schedule. Show less
Vaz, S.C.; Adam, J.A.; Bolton, R.C.D.; Vera, P.; Elmpt, W. van; Herrmann, K.; ... ; Geus-Oei, L.F. de 2022
Purpose 2-[F-18]FDG PET/CT is of utmost importance for radiation treatment (RT) planning and response monitoring in lung cancer patients, in both non-small and small cell lung cancer (NSCLC and... Show morePurpose 2-[F-18]FDG PET/CT is of utmost importance for radiation treatment (RT) planning and response monitoring in lung cancer patients, in both non-small and small cell lung cancer (NSCLC and SCLC). This topic has been addressed in guidelines composed by experts within the field of radiation oncology. However, up to present, there is no procedural guideline on this subject, with involvement of the nuclear medicine societies. Methods A literature review was performed, followed by a discussion between a multidisciplinary team of experts in the different fields involved in the RT planning of lung cancer, in order to guide clinical management. The project was led by experts of the two nuclear medicine societies (EANM and SNMMI) and radiation oncology (ESTRO). Results and conclusion This guideline results from a joint and dynamic collaboration between the relevant disciplines for this topic. It provides a worldwide, state of the art, and multidisciplinary guide to 2-[F-18]FDG PET/CT RT planning in NSCLC and SCLC. These practical recommendations describe applicable updates for existing clinical practices, highlight potential flaws, and provide solutions to overcome these as well. Finally, the recent developments considered for future application are also reviewed. Show less
Couwenberg, A.; Heide, U. van der; Janssen, T.; Triest, B. van; Remeijer, P.; Marijnen, C.; ... ; Nowee, M. 2022
The master protocol trial design aims to increase efficiency in terms of trial infrastructure and protocol administration which may accelerate development of (technical) innovations in radiation...Show moreThe master protocol trial design aims to increase efficiency in terms of trial infrastructure and protocol administration which may accelerate development of (technical) innovations in radiation oncology. A master protocol to study feasibility of techniques/software for MR-guided adaptive radiotherapy with the MR-Linac is described and discussed. Show less
Objective: To assess the efficacy and toxicity of proton radiotherapy in vestibular schwannoma. Study Design: Retrospective chart review and volumetric MRI-analyses. Setting: Tertiary referral... Show moreObjective: To assess the efficacy and toxicity of proton radiotherapy in vestibular schwannoma. Study Design: Retrospective chart review and volumetric MRI-analyses. Setting: Tertiary referral center. Patients: Vestibular schwannoma patients treated with protons between 2003 and 2018. Intervention: Proton radiotherapy. Main Outcome Measures: Tumor control was defined as not requiring salvage treatment. Progressive hearing loss was defined as a decrease in maximum speech discrimination score below the 95% critical difference in reference to the pretreatment score. Hearing assessment includes contralateral hearing and duration of follow-up. Dizziness and/or unsteadiness and facial and trigeminal nerve function were scored. Patients who had surgery prior to proton radiotherapy were separately assessed. Results: Of 221 included patients, 136 received single fraction and 85 fractionated proton radiotherapy. Actuarial 5-year local control rate was 96% (95% CI 90-98%). The median radiological follow-up was 4.5 years. Progressive postirradiation speech discrimination score loss occurred in 42% of patients with audiometric follow-up within a year. Facial paresis was found in 5% (usually mild), severe dizziness in 5%, and trigeminal neuralgia in 5% of patients receiving protons as primary treatment. Conclusions: Proton radiotherapy achieves high tumor control with modest side effects aside from hearing loss in vestibular schwannoma patients. Limited and heterogeneous outcome reporting hamper comparisons to the literature. Potential sequelae of radiation therapy impacting vestibular function, cognitive function, and quality of life warrant further evaluation. Subgroups that benefit most from proton radiotherapy should be identified to optimize allocation and counterbalance its costs. Show less
