Papers by Johannes Langendijk

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Sep 26, 2018
This study investigated whether Magnetic Resonance image biomarkers (MR-IBMs) were associated wit... more This study investigated whether Magnetic Resonance image biomarkers (MR-IBMs) were associated with xerostomia 12 months after radiotherapy (Xer) and to test the hypothesis that the ratio of fat-to-functional parotid tissue is related to Xer. Additionally, improvement of the reference Xer model based on parotid gland dose and baseline xerostomia, with MR-IBMs was explored. Parotid gland MR-IBMs of 68 head and neck cancer patients were extracted from pre-treatment T1-weighted MR images, which were normalized to fat tissue, quantifying 21 intensity and 43 texture image characteristics. The performance of the resulting multivariable logistic regression models after bootstrapped forward selection was compared with that of the logistic regression reference model. Validity was tested in a small external cohort of 25 head and neck cancer patients. High intensity MR-IBM P90 (the 90th intensity percentile) values were significantly associated with a higher risk of Xer. High P90 values were re...

American journal of clinical oncology, Jan 22, 2018
The objective of this review is to discuss factors related to the risk of osteoradionecrosis (ORN... more The objective of this review is to discuss factors related to the risk of osteoradionecrosis (ORN) and how to minimize the likelihood of this complication. A PubMed search for publications pertaining to ORN within the last 3 years was conducted revealing 44 publications. The bibliographies of these publications were reviewed to identify additional references spanning a longer time period. The incidence of ORN is 5% to 10% with a median latency period of 1 to 2 years or less. The likelihood of ORN depends on a number of factors including primary site and extent of disease, dental status, treatment modality, radiotherapy (RT) dose, volume of mandible included in the planning target volume, RT fractionation schedule and technique, and teeth extractions. The risk of ORN may be reduced by limiting the RT dose and volume of mandible irradiated without increasing the risk of a local-regional recurrence due to a marginal miss.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 15, 2017
Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the noto... more Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome. A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies. Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisi...

Cancer Treatment Reviews, 2017
Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck... more Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck. Despite enormous advances in RT planning and delivery, a significant number of patients will experience radiation-associated toxicities, especially those treated with concurrent systemic agents. Many effective management options are available for acute RT-associated toxicities, but treatment options are much more limited and of variable benefit among patients who develop late sequelae after RT. The adverse impact of developing late tissue damage in irradiated patients may range from bothersome symptoms that negatively affect their quality of life to severe lifethreatening complications. In the region of the head and neck, among the most problematic late effects are impaired function of the salivary glands and swallowing apparatus. Other tissues and structures in the region may be at risk, depending mainly on the location of the irradiated tumor relative to the mandible and hearing apparatus. Here, we review the available evidence on the use of different therapeutic strategies to alleviate common late sequelae of RT in head and neck cancer

PloS one, 2016
To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax I... more To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. The robustness criterion was met in the IMRT and minimax IMPT pla...

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2013
In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (acceler... more In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy alone (AR) the prognostic and predictive value of CAIX, a hypoxia-associated protein, was investigated. 261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX. CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival. Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR. Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR (RC 97% vs 71%, p < 0.01 and MFS 92% vs 69%, p = 0.06). Patients with a perinecrotic CAIX staining pattern had a significantly worse local control, metastasis-free and overall survival compared to patients with a diffuse pattern (...
Radiotherapy and Oncology, 2010
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Radiotherapy and Oncology, 2014

Head & Neck, 2010
Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinol... more Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinologists, and skull base surgeons. Recent innovations in surgical and nonsurgical therapeutic modalities raise the question of whether there has been any measurable improvement for treatment outcomes. A retrospective review of data from recent studies that focus on surgery, radiation, and chemotherapy, or combinations thereof, was conducted. Surgery continues to be the preferred treatment and provides the best results, albeit with an inherent bias based on patient selection. For advanced disease (T4 lesions), the survival rate remains only modest. Complications of treatment, including both surgical and radiation therapy, have been reduced. There is a need to improve the efficacy of treatment for this disease. Recommendations for the future direction of therapeutic investigations are outlined.

Head & Neck, 2012
7. Weiss D, Koopmann M, Rudack C. Prevalence and impact on clinicopa-thological characteristics o... more 7. Weiss D, Koopmann M, Rudack C. Prevalence and impact on clinicopa-thological characteristics of human papillomavirus-16 DNA in cervicallymph node metastases of head and neck squamous cell carcinoma.Head Neck 2011;33:856–862.8. Armas GL, Su CY, Huang CC, Fang FM, Chen CM, Chien CY. Theimpact of virus in N3 node dissection for head and neck cancer. EurArch Otorhinolaryngol 2008;265:1379–1384.9. Barwad A, Sood S, Gupta N, Rajwanshi A, Panda N, Srinivasan R.Human papilloma virus associated head and neck cancer: a PCR basedstudy. Diagn Cytopathol 2011;Epub ahead of print.10. Hoffmann M, Gottschlich S, G€or €ogh T, et al. Human papillomaviruses inlymph node neck metastases of head and neck cancers. Acta Otolaryngol2005;125:415–421.11. Desai PC, Jaglal MV, Gopal P, et al. Human papillomavirus in metastaticsquamous carcinoma from unknown primaries in the head and neck: a ret-rospective 7 year study. Exp Mol Pathol 2009;87:94–98.12. Compton AM, Moore-Medlin T, Herman-Ferdinandez L, et al. Humanpapillomavirus in metastatic lymph nodes from unknown primary headand neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2011;145:51–57.

European Archives of Oto-Rhino-Laryngology, 2012
The management of head and neck squamous cell carcinomas does not end with the completion of abla... more The management of head and neck squamous cell carcinomas does not end with the completion of ablative therapy. The oncologic objectives of post-treatment follow-up are to detect recurrences and second primary tumors; beyond that, follow-up should evaluate acute and chronic treatment-related side effects, guide the rehabilitation process, alleviate functional loss, manage pain, restore nutritional status and assess psychosocial factors. In this structured review, we address the questions of timing and the tools required to achieve a complete and coherent routine surveillance. Several guidelines and consensus statements recommend clinical examination as the cornerstone of follow-up which should be performed for at least 5 years, although there are no data in favor of any one particular follow-up program, and only low-level evidence suggests an improvement in oncologic outcomes by close follow-up. Baseline imaging (computed tomography and This paper was written by members and invitees of the International Head and Neck Scientific Group (http://www.IHNSG.com).

European Archives of Oto-Rhino-Laryngology, 2012
Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive trac... more Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the rehabilitation process, and to provide psychosocial support when needed. To our knowledge, there are no published reports in the literature dedicated to the follow-up of patients with these tumours. A comprehensive literature search for post-treatment follow-up strategies spanning from 1980 to 2012 was performed on several databases. This review focuses on malignant salivary gland tumors, soft tissue sarcomas, cutaneous squamous cell carcinomas, and sinonasal adenocarcinomas. Given the varying biological behavior and treatment-related factors and based on the literature, different recommendations are made on the follow-up of patients with the above-mentioned tumors.

Cancer, 2006
In this prospective study, the effects of a second course of postoperative radiation therapy on l... more In this prospective study, the effects of a second course of postoperative radiation therapy on locoregional control, survival, toxicity, and quality of life were investigated in patients who underwent resection of a second primary or locoregional recurrent head and neck tumor in a previously irradiated area. In total, 39 patients who underwent surgery for second primary tumors (n ϭ 19 patients) or for recurrent locoregional tumors (n ϭ 20 patients) were retreated with postoperative radiotherapy (RE-PORT). Indications for RE-PORT were extranodal spread (49%), positive surgical margins (44%), and/or other risk factors (8%). The target volume for RE-PORT was confined to the high-risk area. No elective radiotherapy was applied in regions that were situated in the formerly high-dose area. A total dose of 46 grays (Gy) was given to elective areas with boosts from 60 Gy to 66 Gy to the high-risk region with conventional fractionation. The results of RE-PORT were compared with the results from patients who were treated in the same period with primary adjuvant radiotherapy (PRI-PORT) at the authors' institution. The mean follow-up was 32 months (range, 3-84 mos). The locoregional control rate after 3 years in the RE-PORT group was 74%, and the 3-year overall survival rate was 44%. This did not differ significantly compared with survival rates in the PRI-PORT group. Although a higher rate of late radiation-induced morbidity and more head and neck symptoms were observed in the RE-PORT group compared with the PRI-PORT group, no differences were observed with regard to the more general dimensions of quality of life. CONCLUSIONS. RE-PORT after surgery for recurrent locoregional tumors and/or second primary tumors should be considered in patients who have high-risk histopathologic features.

Acta Oncologica, 2010
Purpose/background-Validating a predictive model for late rectal bleeding following external beam... more Purpose/background-Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). Material and methods-One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/ fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Results-Late rectal bleeding (>=grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m = 0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p = 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ 2 test (p = 0.44).
Oral Oncology, 2012
Distant metastases from head and neck squamous cell carcinoma (HNSCC), though rare at initial pre... more Distant metastases from head and neck squamous cell carcinoma (HNSCC), though rare at initial presentation, remain an important manifestation of cancer recurrence and mortality. Although generally considered incurable with a dismal prognosis despite palliative therapy, highly selected patients with distant metastases may have a long term survival benefit from aggressive surgery or radiotherapy. Advances in systemic treatments also may improve patient survival. This article reviews the current state of management of HNSCC patients with distant metastases.
JOURNAL OF INDIAN AND BUDDHIST STUDIES (INDOGAKU BUKKYOGAKU KENKYU), 1968

Radiotherapy and Oncology, 2015
A risk model, the total dysphagia risk score (TDRS), was developed to predict which patients are ... more A risk model, the total dysphagia risk score (TDRS), was developed to predict which patients are most at risk to develop grade ⩾2 dysphagia at 6months following radiotherapy (RT) for head and neck cancer. The purpose of this study was to validate this model at 6months and to investigate the power at earlier and later time-points. A second aim was to see if this model can be used in a partially accelerated RT regimen. 164 patients from 3 different centres treated with RT between 2008 and 2014 were included in the current study. Both physician-scored dysphagia and QoL data were prospectively obtained. The TDRS of all patients was correlated with the physician-scored dysphagia and the QoL data. To validate this prediction model, we tested the validity in terms of calibration and discrimination. Partial acceleration had no influence on the TDRS. Regarding physician-scored dysphagia, there was a significant correlation with dysphagia grade ⩾2 at 1, 3, 6 and 9months. The area-under-the-curve at 1month was 0.85; at 3months 0.80; at 6months 0.85; at 9months 0.86 and 0.79 at 12months. Regarding QoL, TDRS correlates with PEG-tube usage at 6 and 12months. We found significant correlations between TDRS and dysphagia grade ⩾2 and PEG-tube usage.
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Papers by Johannes Langendijk