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
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
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
Dekker, H.; Schulten, E.A.J.M.; Ruijven, L. van; Essen, H.W. van; Blom, G.J.; Bloemena, E.; ... ; Bravenboer, N. 2020
Objectives: The aim of this study was to assess the microarchitecture and turnover in irradiated cancellous mandibular bone and the relation with radiation dose, to elucidate the effects of... Show moreObjectives: The aim of this study was to assess the microarchitecture and turnover in irradiated cancellous mandibular bone and the relation with radiation dose, to elucidate the effects of radiotherapy on the mandible.Patients and methods: Mandibular cancellous bone biopsies were taken from irradiated patients and controls. Micro-CT scanning was performed to analyze microstructural bone parameters. Bone turnover was assessed by histomorphometry. Local radiation dose at the biopsy site (Dmax) was estimated from radiotherapy plans.Results: Twenty-seven irradiated patients and 35 controls were included. Osteoid volume (Osteoid Volume/Bone Volume, OV/BV) [0.066/0.168 (median/interquartile range (IQR), OV/BV; %), P < 0.001], osteoid surface (Osteoid Surface/Bone Surface, OS/BS) [0.772/2.17 (median/IQR, OS/BS; %), P < 0.001] and osteoclasts number (Osteoclasts per millimetre bone surface, Ocl/mmBS; mm(2)) [0.026/0.123 (median/IQR, Ocl/mmBS; mm2), P < 0.001] were decreased; trabecular number (Tb.N) was lower [1.63/0.63 (median/IQR, Tb.N; 1/mm(-1)), P = 0.012] and trabecular separation (Tb.Sp) [0.626/0.24 (median/IQR, Tb.Sp; mu m), P = 0.038] was higher in irradiated mandibular bone. With higher Dmax, trabecular number increases (Spearman's correlation R = 0.470, P = 0.018) and trabecular separation decreases (Spearman's correlation R = -0.526, P = 0.007). Bone mineral density (BMD, milligrams hydroxyappetite per cubic centimetre, mgHA/cm(3)) [1016/99 (median/IQR, BMD; mgHA/cm(3)), P = 0.03] and trabecular separation [0.739/0.21 (median/IQR, Tb.Sp; mu m), P = 0.005] are higher whereas connectivity density (Conn Dens) [3.94/6.71 (median/IQR, Conn Dens), P = 0.047] and trabecular number [1.48/0.44 (median/IQR, Tb.N; 1/mm(-1)), P = 0.002] are lower in Dmax <= 50 Gy compared to controls.Conclusions: Radiotherapy dramatically impairs bone turnover in the mandible. Deterioration in microarchitecture only affects bone irradiated with a Dmax of <50 Gy. The 50 Gy value seems to be a critical threshold to where the effects of the radiation is more detrimental. (C) 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. Show less
Background and aim: External beam radiotherapy (EBRT) combined with brachytherapy has an essential role in the curative treatment of primary vaginal cancer. EBRT is associated with significant... Show moreBackground and aim: External beam radiotherapy (EBRT) combined with brachytherapy has an essential role in the curative treatment of primary vaginal cancer. EBRT is associated with significant tumour shrinkage, making primary vaginal cancer suitable for image guided adaptive brachytherapy (IGABT). The aim of these recommendations is to introduce an adaptive target volume concept for IGABT of primary vaginal cancer.Methods: In December 2013, a task group was initiated within GYN GEC-ESTRO with the purpose to introduce an IGABT target concept for primary vaginal cancer. All participants have broad experience in IGABT and vaginal cancer brachytherapy. The target concept was elaborated as consensus agreement based on an iterative process including target delineation and dose planning comparison, retrospective analysis of clinical data and expert opinions.Results: Gynaecological examination and MR imaging are the modalities of choice for local tumour assessment. A specific template for standardised documentation with clinical drawings for vaginal cancer was developed. The adaptive target volume concept comprises different response-related target volumes. For EBRT these are related to the primary tumour and the lymph nodes, while for IGABT these are related to the primary tumour and are consisting of the residual gross tumour volume (GTV-Tres) and the high-, and intermediate risk clinical target volumes (CTV-THR, CTV-TIR).Conclusion: This target concept for IGABT of primary vaginal cancer defines adaptive target volumes for volumetric dose prescription and should improve comparability of different radiotherapy schedules of this rare disease. A prospective evaluation of the target volume concept within a multicentre study is planned. (C) 2019 Elsevier B.V. All rights reserved. Show less
Immunotherapy has obtained a secure place in the treatment of metastatic non-small cell lung cancer (NSCLC) and has made a great impact on prognosis of responders. Unfortunately, not all NSCLC... Show moreImmunotherapy has obtained a secure place in the treatment of metastatic non-small cell lung cancer (NSCLC) and has made a great impact on prognosis of responders. Unfortunately, not all NSCLC patients derive benefit from this treatment. Several immune escape mechanisms have been postulated, explaining failure of tumor immune attack. A better understanding of these mechanisms helps us to seek treatment strategies to overcome resistance to immunotherapy. Radiotherapy has immunomodulatory qualities capable of enhancing the anticancer immune response by tackling a number of these tumor escape mechanisms. In this review, we focus on mechanisms of off-target effects of radiotherapy, the so-called abscopal effect, by describing the current role of immune checkpoint inhibitors (ICIs) in NSCLC, the possible reasons for its failures and evidence on how radiotherapy may be able to counteract these mechanisms. An oversight of pre-clinical and clinical data supporting augmentation of abscopal events by radiotherapy when combined with ICIs is presented. As much remains unclear regarding optimal dose, fractionation, target volume or timing of radiation therapy, future research will need to focus on implementing data from pre-clinical and translational findings in the development of new clinical trials in order to help optimizing the potential of the combination of immunotherapy with radiotherapy. Show less
Introduction: The revised Dutch colorectal cancer guideline (2014), led to an overall decrease in preoperative radiotherapy (RT) use. This study evaluates hospital variation in RT use for... Show moreIntroduction: The revised Dutch colorectal cancer guideline (2014), led to an overall decrease in preoperative radiotherapy (RT) use. This study evaluates hospital variation in RT use for resectable rectal cancer and the influence of guideline revision, including the nationwide impact of changing RT application on short term outcomes.Methods: Data of surgically resected rectal cancer patients registered in the Dutch ColoRectal Audit were extracted between 2011 and 2017. Patients were divided into groups based on time of guideline revision (<2014 and >= 2014). Primary outcome was guideline adherence at hospital level regarding RT application, stratified for three stage groups. Secondary outcomes included positive circumferential resection (CRM+) and 30-day complicated postoperative course.Results: The groups consisted of 7364 and 12,057 patients, respectively. In total, 6772 patients did not receive RT (17.6% (<2014) vs. 45.7% (>= 2014), p < 0.001). The largest increase of surgery alone was observed for cT1-2N0 stage rectal cancer (35.1% vs. 91.8%, p < 0.001), with a substantial decrease in hospital variation (IQR 22.2-50.0% vs. IQR 87.6-98.0%). For cT1-3N1MRF-stage rectal cancer, a substantial amount of hospital variation in short course RT remained after guideline revision (IQR 26.8-54.1% vs. IQR 26.2-50.0%). A significant decrease in CRMthorn (5.8% vs. 4.2%, p < 0.001) and complicated course (22.5% vs. 18.5%, p < 0.001) was observed.Conclusions: Radiotherapy for early-stage rectal cancer was uniformly abandoned after guideline revision, while substantial hospital variation remained for intermediate risk resectable rectal cancer in the Netherlands. The substantial nationwide decrease in the use of RT for rectal cancer treatment did not negatively impact CRM involvement. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Objective Vestibular schwannomas are benign tumors that are often managed by radiotherapy. Minimizing long-term toxicity is paramount for a population that remains at normal life expectancy and at... Show moreObjective Vestibular schwannomas are benign tumors that are often managed by radiotherapy. Minimizing long-term toxicity is paramount for a population that remains at normal life expectancy and at risk for loss of quality of life for years if not decades. Whereas current radiotherapy standard utilizes photon radiation, proton radiotherapy characteristics may enable a reduction of toxicity by reducing the volume of collateral irradiated healthy tissue. A systematic review was conducted to assess tumor control and short- and long-term sequelae after proton irradiation. Methods Studies that reported on treatment outcomes of proton radiotherapy in vestibular schwannoma patients were included. Results Five peer-reviewed retrospective series met the inclusion criteria. Quality of the studies varied from low to good. There were 276 unique patients described. Tumor control rates ranged from 85 to 100% (radiological median follow-up of 2.2-7.4 years). Hearing loss rates, defined as losing Gardner Robertson class I/II hearing, showed an weighted crude average 52% (depending on follow-up duration). The weighted averages for post-irradiation facial and trigeminal neuropathy were 5% and 4%, respectively. The risk of neuropathy seems to decrease with lower radiation dosages. Conclusion Proton irradiation for vestibular schwannomas achieves high tumor control rates, equivalent to photon irradiation. Reported cranial nerve preservation rates vary, partly due to an apparent selection bias with a high percentage of patients with clinical symptoms prior to treatment. Results of cranial nerve function preservation, quality of life, and cognitive functioning are currently insufficiently reported. In addition, advances in proton radiotherapy technology warrant re-evaluation of current techniques and protocols for the management of vestibular schwannomas. Show less
Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME... Show moreIntroduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p < 0.001). Initial CRM positivity and palliative intent treatment were associated with worse OS after LRRC, while prior PRT was not.Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Aims: The purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS)... Show moreAims: The purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS).Patients & methods: In this retrospective cohort study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery were identified from a prospectively maintained database. A wound complication (WC) was defined as any local complication of the surgical area requiring intervention, hospital readmission or significant extension of the initial admission period.Results: A total of 191 preoperatively irradiated ESTS patients were included in this study. WC was seen in 31% of the patients (n=60). WC started after a median time of 25 days from surgery, with a median duration of 76 days. Adiposity, smoking and a lower extremity or superficial tumor localization were significantly correlated with an increased WC rate. Risk factors for a duration of WC >= 120 days are early development of WC (<= 21 days after surgery) and smoking. Local control rates after 1, 3 and 5 years were 99%, 93% and 93%, respectively.Conclusion: Approximately one-third of patients selected for preoperative RT develops a WC, typically in smoking, adipose patients with superficial tumor localizations in the lower extremity. Based upon the well-established superior long-term functional outcome, maintained excellent local control rates and the temporary nature of the WC issue, preoperative RT remains our preferred treatment. Although, in patients at high risk of WC, post-operative RT might be considered. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Endometrial cancer is the most common gynecological malignancy in high-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur.... Show moreEndometrial cancer is the most common gynecological malignancy in high-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (with ongoing studies of sentinel node biopsy) enables identification of lymph node positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant radiotherapy is used for Stage I-II patients with high-risk factors and Stage III lymph node negative patients. In advanced disease, a combination of surgery to no residual disease and chemotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval. Show less
Background and purpose: Radiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy... Show moreBackground and purpose: Radiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy in children (<18 years) and investigated correlations with patient and treatment related characteristics. Material and methods: Between 2010 and 2016, 34 children received radiotherapy involving the thoracic region. We delineated heart contours and measured heart volumes on 114 CBCTs. Relative volume changes were quantified with respect to the volume on the first CBCT (i.e., 100%). Cardiac radiation dose parameters expressed as 2 Gy/fraction equivalent doses were calculated from DVHs. Chemotherapy was categorized as treatment with anthracyclines, alkylating agents, vinca-alkaloids, and other. Results: The overall median heart volume reduction from the first to the last CBCT was 5.5% (interquartile range1.6-9.7%; p < 0.001). Heart volumes decreased significantly between the baseline measurement and the first week (Bonferroni's adjusted p = 0.002); volume changes were not significant during the following weeks. Univariate analysis showed a significant correlation between heart volume reduction and alkylating agents; however, no multivariate analyses could be done to further confirm this. Conclusions: We found a significant heart volume reduction in children during radiotherapy. Elucidation of underlying mechanisms, clinical relevance, and possible long-term consequences of early heart volume reduction require a prospective follow-up study. (C) 2018 Elsevier B.V. All rights reserved. Show less
Wink, K.C.J.; Roelofs, E.; Simone, C.B.; Dechambre, D.; Santiago, A.; Stoep, J. van der; ... ; Troost, E.G.C. 2018
Purpose: To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison... Show morePurpose: To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial.Methods: For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions.Results: The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ.Conclusion: On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient. (C) 2018 Elsevier B.V. All rights reserved. Show less
