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BACKGROUND: Normal-tissue complication probability (NTCP) models predict complication risk in patients receiving radiotherapy, considering radiation dose to healthy tissues, and are used to select patients for proton therapy, based on their expected reduction in risk after proton therapy versus photon radiotherapy (ΔNTCP). Recommended model evaluation measures include area under the receiver operating characteristic curve (AUC), overall calibration (CITL), and calibration slope (CS), whose precise relation to patient selection is still unclear. We investigated how each measure relates to patient selection outcomes.METHODS: The model validation and consequent patient selection process was simulated within empirical head and neck cancer patient data. By manipulating performance measures independently via model perturbations, the relation between model performance and patient selection was studied.RESULTS: Small reductions in AUC (-0.02) yielded mean changes in ΔNTCP between 0.9-3.2%, and single-model patient selection differences between 2-19%. Deviations (-0.2 or +0.2) in CITL or CS yielded mean changes in ΔNTCP between 0.3-1.4%, and single-model patient selection differences between 1-10%.CONCLUSIONS: Each measure independently impacts ΔNTCP and patient selection and should thus be assessed in a representative sufficiently large external sample. Our suggested practical model selection approach is considering the model with the highest AUC, and recalibrating it if needed.

Background and purpose: A comprehensive individual toxicity risk profile is needed to improve radiation treatment optimisation, minimising toxicity burden, in head and neck cancer (HNC) patients. We aimed to develop and externally validate NTCP models for various toxicities at multiple time points.Materials and methods: Using logistic regression, we determined the relationship between normal tissue irradiation and the risk of 22 toxicities at ten time points during and after treatment in 750 HNC patients. The toxicities involved swallowing, salivary, mucosal, speech, pain and general complaints. Studied pre-dictors included patient, tumour and treatment characteristics and dose parameters of 28 organs. The resulting NTCP models were externally validated in 395 HNC patients.Results: The NTCP models involved 14 organs that were associated with at least one toxicity. The oral cavity was the predominant organ, associated with 12 toxicities. Other important organs included the parotid and submandibular glands, buccal mucosa and swallowing muscles. In addition, baseline toxicity, treatment modality, and tumour site were common predictors of toxicity. The median discrimination performance (AUC) of the models was 0.71 (interquartile range: 0.68-0.75) at internal validation and 0.67 (interquartile range: 0.62-0.71) at external validation.Conclusion: We established a comprehensive individual toxicity risk profile that provides essential insight into how radiation exposure of various organs translates into multiple acute and late toxicities. This comprehensive understanding of radiation-induced toxicities enables a new radiation treatment optimisation concept that balances multiple toxicity risks simultaneously and minimises the overall tox-icity burden for an individual HNC patient who needs to undergo radiation treatment. (C) 2021 The Author(s). Published by Elsevier B.V.

ObjectivesGiven the difficulties in diagnosing and treating head-and-neck cancer, care is centralised in the Netherlands in eight head-and-neck cancer centres and six satellite regional hospitals as preferred partners. A requirement is that all patients of the partner should be discussed in a multidisciplinary team meeting (MDT) with the head-and-neck centre as part of a Dutch health policy rule. In this mixed-method study, we evaluate the value that the video-conferenced MDT adds to the MDTs in the care pathway, quantitative regarding recommendations given and qualitative in terms of benefits for the teams and the patient.DesignA sequential mixed-method study.SettingOne oncology centre and its partner in the Northern part of the Netherlands.ParticipantsHead-and-neck cancer specialists presenting patient cases during video-conferenced MDT over a period of 6 months. Semistructured interviews held with six medical specialists, three from the centre and three from the partner.Primary and secondary outcome measuresPercentage of cases in which recommendations were given on diagnostic and/or therapeutic plans during video-conferenced MDT.ResultsIn eight of the 336 patient cases presented (2%), specialists offered recommendations to the collaborating team (three given from centre to partner and five from partner to centre). Recommendations mainly consisted of alternative diagnostic modalities or treatment plans for a specific patient. Interviews revealed that specialists perceive added value in discussing complex cases because the other team offered a fresh perspective by hearing the case ‘as new’. The teams recognise the importance of keeping their medical viewpoints aligned, but the requirement (that the partner should discuss all patients) was seen as outdated.ConclusionsThe added value of the video-conferenced MDT is small considering patient care, but the specialists recognised that it is important to keep their medical viewpoints aligned and that their patients benefit from the discussions on complex cases.

Background The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years. Methods Patients with inoperable squamous cell carcinoma (SCC) of the oropharynx, oral cavity, or hypopharynx, were randomized between radiotherapy (RT) + IA cisplatin 150 mg/m2, followed by systemic rescue or RT + I.V. cisplatin 100 mg/m2. RT consisted of 46 Gy to the affected and elective areas, followed by a boost of 24 Gy. Results Among 237 patients, 57 recurred locally, 35 regionally, and 80 locoregionally. There were 32 second primary tumors, 65 distant metastases, and 154 deaths. Locoregional control and overall survival were not different between the treatment arms. Late dysphagia was worse in the I.V. arm (log-rank p = .014). Conclusion IA cisplatin did not improve tumor control compared to I.V. administered cisplatin, despite the higher dose in IA delivery of the drug. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years.Patients with inoperable squamous cell carcinoma (SCC) of the oropharynx, oral cavity, or hypopharynx, were randomized between radiotherapy (RT) + IA cisplatin 150 mg/m(2) , followed by systemic rescue or RT + I.V. cisplatin 100 mg/m(2) . RT consisted of 46 Gy to the affected and elective areas, followed by a boost of 24 Gy.Among 237 patients, 57 recurred locally, 35 regionally, and 80 locoregionally. There were 32 second primary tumors, 65 distant metastases, and 154 deaths. Locoregional control and overall survival were not different between the treatment arms. Late dysphagia was worse in the I.V. arm (log-rank p = .014).IA cisplatin did not improve tumor control compared to I.V. administered cisplatin, despite the higher dose in IA delivery of the drug. © 2015 Wiley Periodicals, Inc. Head Neck 38: E488-E493, 2016.

Purpose : Prevention of damage to critical normal tissues is of paramount importance for the quality of life of patients irradiated for cancers in the head and neck. The purpose of this paper was to evaluate the parotid gland sparing 3D conformal radiation therapy technique (3DCRT) in a prospective study in node negative cancer of the larynx. Materials and methods : Twenty-six patients with node negative squamous cell cancer of the larynx were irradiated by a 3DCRT technique (class solution) to both sides of the neck (elective dose 46 Gy to levels II, III and IV) and primary tumour (70 Gy). Dose distributions of the major salivary glands were correlated with objective (stimulated whole saliva flow, WS) and subjective (questionnaire; visual analogue scale, VAS) salivary gland function. Apart from the clinically used 3DCRT technique, in order to optimise 3DCRT dose distributions, intensity modulated (IMRT) treatment plans were generated for the same patient population. Dose–volume histograms of 3DCRT and IMRT treatment plans were analysed and compared. Results : For the 26 patients irradiated with the 3DCRT class solution technique: VAS scores and questionnaires reached their nadir 3 months post-radiotherapy; WS reached its nadir 6 months post-radiotherapy. WS flow rates improved significantly, but never normalised; 2 years post-treatment WS measurements were 48% of the pre-treatment values. VAS scores deteriorated during ERT from 0 pre-treatment to 6.1 immediately post-treatment. Compared to pre-treatment, questionnaires were answered affirmative by increasing numbers of patients. For all patients, IMRT treatment plans resulted in a significant reduction of the dose delivered to the parotid glands compared to the 3DCRT-treatment technique. Conclusions : The class solution for the 3DCRT salivary gland sparing technique is inadequate for fully preserving salivary gland function, given the dose distributions (DVHs) as well as the subjective- and objective salivary gland function assessments. The results can be optimised in the future, that is a further reduction of xerostomia can be achieved, by using IMRT techniques focused at sparing major and minor salivary glands.

Purpose : The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). Materials and methods : Ninety-one patients with primary stage I–IVB NPC, were treated between 1991 and 2000 with 60–70Gy external beam radiation therapy (ERT) followed by 11–18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III–IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). Results : For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. Conclusions : The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

Background. Xerostomia can have a significant impact on the quality of life of patients treated by radiation therapy (RT) for cancer in the head and neck. The first aim of the study was to evaluate the degree of xerostomia in 39 long-term survivors treated between 1965-1995 by conventional two-dimensional radiation therapy and currently without evidence of disease. The second aim was to develop a concise instrument to evaluate the subjective aspects of xerostomia. Methods. A newly developed questionnaire and a visual analog scale (VAS) were used in analyzing the degree of dry mouth and xerostomia-related problems. The radiation dose received by the major salivary glands was estimated by analyzing two-dimensional simulation films. Results. Sixty-four percent of the patients experienced a moderate to severe degree of xerostomia. In the multivariate analysis, three questions regarding dry mouth, eating, and speech were particularly discriminatory for establishing the degree of xerostomia as expressed by the VAS score. Conclusions. In this survey, 64% of the long-term survivors, after treatment by conventional two-dimensional radiation therapy for a malignancy in the head and neck region, still experienced a moderate to severe degree of permanent xerostomia. A simplified instrument to evaluate xerostomia subjectively can consist of the VAS score and three graded questions.

Introduction: The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume (PTV). Methods: For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To) and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans, consisting of lateral parallel opposed beams, were used for irradiation of both the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for each tumor a 3-D conformal treatment plan was developed using the 3-D computer planning system, CadPlan, and Optimize, a noncommercial program to compute optimal beam profiles. Beam angles were selected with the intention of optimal sparing of the salivary glands. The intensity of the beams was then modulated to achieve a homogeneous dose distribution in the target for the given 3D-CRT techniques. The dose distributions, dose–volume histograms (DVHs) of target and salivary glands, tumor control probabilities (TCPs), salivary gland volumes absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal tissue complication probabilities (NTCPs) of each treatment plan were computed. The parameters of the 3D-CRT plans were compared with those of the conventional plans. Results: In comparison with the conventional technique, the dose homogeneity in the target volume was improved by the conformal technique for both tumor sites. In addition, for the SgL conformal technique, the average volumes of the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%, and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%, respectively. For the To conformal techniques, the V40 of the parotid glands was decreased on average by 31%, resulting in an average reduction of the NTCP by 49%. Both the average V50 and the NTCP of the submandibular glands were decreased by 7%. Conclusion: For primary tumors of the oropharynx, the parotid glands could be spared to a considerable degree with the 3D-CRT technique. However, particularly the ipsilateral submandibular gland could not be spared. For primary tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands to a considerable and probably clinically relevant degree. Moreover, the conformal techniques resulted in an increased dose homogeneity in the PTV of both tumor sites.

Introduction: Elective treatment of the clinically node-negative neck by radiation results in excellent control rates. However, radiation therapy with its organ-preserving properties is not without morbidity. Side effects of elective neck irradiation are mainly due to damage of the major and minor salivary glands, resulting in the dry mouth syndrome. Given that RT is the preferred treatment modality in case of elective treatment of the neck in many institutions, it is of utmost importance to try and reduce the associated sequelae of RT. Material and Methods: With the introduction of CT-planning systems and the development of 3D conformal radiation therapy (3D CRT) techniques, it has become feasible to deliver adequate doses of radiation to the target (neck) and at the same time saving (parts of) the salivary glands from doses beyond tolerance. A prerequisite for these techniques is that they require a precise knowledge of the target (i.e., of the elective neck) on CT. To be able to correlate borders of the surgical levels in the neck (I–VI) with structures seen on CT, an anatomical study, using two fixed (phenol, formaldehyde) human cadavers, was performed. Subsequently, the 6 potential lymph node regions in the neck on CT were defined. Results and Discussion: The reference for the current 3D CT-based definition of the lymph node regions in the neck is the official report of the American Academy of Otolaryngology, describing, based on surgical anatomy, the lymph node groups in the neck by Levels I–VI. The present investigation depicts reproducible landmarks on transversal CT images, corresponding to anatomical reference structures known from surgical levels (I–VI) and, this way, CT-based lymph node regions (1–6) were constructed.

A case history of unanticipated radiation-induced bilateral optic neuropathy, 18 months after induction chemotherapy and radiation therapy for a locally advanced nasopharyngeal carcinoma, is presented. Retrospective reanalysis of the radiation therapy technique, with emphasis on the doses received by the optic pathway structures, was performed. These re-calculations revealed unexpectedly high doses in the range 79 to 82 Gy (cumulative external and brachytherapy dose) at the level of the optic nerves, which explained the observed radiation injury.Routine implementation of computed tomography for 3D dose planning purposes is therefore advocated. Review of the current literature confirms the importance of 3D dose planning in avoiding this complication and high-lights the role of MRI in establishing the diagnosis of radiation-induced optic neuropathy.

Background. Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of primary tumor volume for advanced head and neck squamous cell carcinoma (HNSCC) treated with CCRT. Methods. Three hundred sixty patients treated with definitive CCRT for advanced HNSCC were selected. The pretreatment MRI or CT scan was used to calculate the primary tumor volume. Median follow-up was 19.8 months. Results. The average primary tumor volume was 37.0 cm(3) (range, 2.1-182.7 cm(3); median, 28.7 cm(3)). Multivariate analysis showed a significant effect of tumor volume on local control. The hazard ratio for a local recurrence increased by 14% per 10 cm(3) volume increase (95% CI, 8% to 21%). There was no significant independent effect of T and N status on local control. Conclusion. For advanced HNSCC, tumor volume is more powerful for predicting outcome after CCRT than TNM status. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 375-382, 2011

Prevention of damage to critical normal tissues is of paramount importance for the quality of life of patients irradiated for cancers in the head and neck. The purpose of this paper was to evaluate the parotid gland sparing 3D conformal radiation therapy technique (3DCRT) in a prospective study in node negative cancer of the larynx.Twenty-six patients with node negative squamous cell cancer of the larynx were irradiated by a 3DCRT technique (class solution) to both sides of the neck (elective dose 46 Gy to levels II, III and IV) and primary tumour (70 Gy). Dose distributions of the major salivary glands were correlated with objective (stimulated whole saliva flow, WS) and subjective (questionnaire; visual analogue scale, VAS) salivary gland function. Apart from the clinically used 3DCRT technique, in order to optimise 3DCRT dose distributions, intensity modulated (IMRT) treatment plans were generated for the same patient population. Dose-volume histograms of 3DCRT and IMRT treatment plans were analysed and compared.For the 26 patients irradiated with the 3DCRT class solution technique: VAS scores and questionnaires reached their nadir 3 months post-radiotherapy; WS reached its nadir 6 months post-radiotherapy. WS flow rates improved significantly, but never normalised; 2 years post-treatment WS measurements were 48% of the pre-treatment values. VAS scores deteriorated during ERT from 0 pre-treatment to 6.1 immediately post-treatment. Compared to pre-treatment, questionnaires were answered affirmative by increasing numbers of patients. For all patients, IMRT treatment plans resulted in a significant reduction of the dose delivered to the parotid glands compared to the 3DCRT-treatment technique.The class solution for the 3DCRT salivary gland sparing technique is inadequate for fully preserving salivary gland function, given the dose distributions (DVHs) as well as the subjective- and objective salivary gland function assessments. The results can be optimised in the future, that is a further reduction of xerostomia can be achieved, by using IMRT techniques focused at sparing major and minor salivary glands.

Purpose: We previously reported our preliminary experience with nasopharyngeal cancer boosted after 60-70 Gy external beam radiotherapy (EBRT) by fractionated endocavitary brachytherapy (ECBT) to cumulative doses of 78-82 Gy. As for Stage III-IVB disease, cisplatin (CDDP)-based neoadjuvant chemotherapy (CHT) was given. The aim of the present study was to define the role of ECBT more accurately. Methods and Materials: Ninety-one patients with primary nasopharyngeal cancer, staged according to the 1997 UICC/AJCC classification system, were treated between 1991 and 2000 with 60-70 Gy external beam radiotherapy and 11-18 Gy ECBT. Of the 91 patients, 21 were treated in conjunction with CHT and 70 without CHT. Tumors were subdivided into undifferentiated (UD) and well, moderately, and poorly differentiated (WMP-D) subtypes. Treatment results were analyzed for local control (LC), disease-free survival (DFS), freedom from distant metastasis, and overall survival (OS). Results: A univariate and multivariate Cox regression analysis found stage, treatment period, age, and grade significant for LC, DFS, and OS. At 2 years, for Stage I-IIB (1st period, 1991-1996), the LC, DFS, and OS were 96%, 88%, and 80%, respectively, vs. 65%, 46%, and 52% for Stage III-IVB. For the 2nd treatment period (1996-2000; CHT for Stage III-IVB), the LC, DFS, and OS at 2 years was 100%, 90%, and 61% (Stage I-IIB), respectively, vs. 86%, 74%, and 66% (Stage III-IVB). Three prognostic groups (PGs) were constructed. For the 1991-1996 period, at 2 years, patients in the good PG (UD Stage I-IIB disease) had 100% LC and 92% OS; those in the intermediate PG (UD Stage III-IVB or WMP-D Stage I-IIB), had 94% LC and 71% OS; and those in the poor PG (WMP-D Stage III-IVB) had 47% LC and 40% OS. For the 1996-2000 period, at 2 years, the good PG had 100% LC and 88% OS; the intermediate PG had 100% LC and 64% OS; and the poor PG had 71% LC and 60% OS. Conclusion: For Stage I-IIB disease treated between 1991 and 2000, at 3 years, the LC and OS was 97% and 67%, respectively. The results with 77-81 Gy without CHT warrant EBRT combined with ECBT to remain our standard of care for Stage I-IIB disease. For N2-3 and/or T3-4 tumors, in addition to high doses of RT, neoadjuvant CHT was administered as of 1996. For the 1991-2000 period, at 3 years, the LC was 86% and the OS was 72% with CHT, with little extra morbidity; they were 68% and 35% without CHT. Because of better target coverage and sparing, T3-4 tumors are currently boosted by stereotactic RT to 81.2 Gy.

Purpose: The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria (AGNB) play a crucial role in the pathogenesis of radiation-induced mucositis; consequently, selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis. Methods and Materials: Head-and-neck cancer patients, when scheduled for treatment by external beam radiation therapy (EBRT), were randomized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E, tobramycin, and amphotericin B (PTA group). Weekly, the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted. The primary study endpoint was the mucositis grade after 3 weeks of EBRT. Results: Seventy-seven patients were evaluable. No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms ( p = 0.33). The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group ( p = 0.01). However, complete eradication of AGNB was not achieved. Conclusions: Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis.

Introduction and purpose : Using three dimensional (3D) conformal radiotherapy (CRT) techniques for elective neck irradiation (ENI) may allow for local disease control to be maintained while diminishing xerostomia by eliminating major salivary glands (or parts thereof) from the treatment portals. The standardization of CT based target volumes for the clinically negative (elective) neck is a prerequisite for 3DCRT. The aim of the present study was to substantially modify an existing (‘original') CT-based protocol for the delineation of the neck target volume, into a more practical (‘simplified') protocol. This will allow for rapid contouring and the implementation of conformal ENI in routine clinical procedures. Material and Methods : An earlier (‘original') version of the CT-based definition for elective neck node regions 2–5 was re-evaluated, using 15 planning CT scans of previously treated patients. The contouring guidelines were simplified by (1) using a smaller number of easily identifiable soft tissue- and bony anatomical landmarks, which in turn had to be identified in only a limited number of CT slices, and (2) by subsequently interpolating the contoured lymph node regions. The adequacy of target coverage and the sparing using both ‘original' and ‘simplified' delineation protocols was evaluated by DVH analysis after contouring the primary tumor, the neck and the major salivary glands in a patient with supraglottic laryngeal (SGL) carcinoma who was treated using a 3DCRT technique. Results: The BEV projections of the ‘original' and the ‘simplified' versions of the 3D elective neck target showed good agreement and were found to be reproducible. The DVH's of the target and parotid glands were not significantly different using both contouring protocols. Conclusions: The ‘simplified' protocol for the delineation of the 3D elective neck target produced both comparable target coverage and sparing of the major salivary glands. When used together with an interpolation program, this ‘simplified' protocol substantial reduced the contouring time and makes ENI with sparing of the major salivary glands a practical and achievable goal.

Brachytherapy and external irradiation combined are an alternative to surgery in the treatment of advanced esophageal cancer. Endosonography has proved to be an accurate method of staging the depth of tumor invasion of esophageal cancer. Sixty-three patients with inoperable esophageal cancer underwent endosonography followed by combined brachytherapy and external irradiation. Staging was incomplete in 31 of 63 patients because of tight stenosis or difficulty in imaging celiac lymph nodes. During follow-up of 23 patients, reduction of tumor thickness and lymph node abnormalities was observed in 16. The median survival was 10.4 months. Survival time was correlated with initial number of metastatic lymph nodes found by endosonography. Paradoxically, the survival of patients with more extensive intra-luminal tumor growth was significantly better than survival of those with less tumor growth. In summary, the response to combined brachytherapy and external irradiation could accurately be assessed with endosonography. Lymph node abnormalities and tumor thickness were closely related to survival rate. (Gastrintest Endosc 1994;40:304-10.)

Contains fulltext : 173061.pdf (Publisher’s version ) (Open Access) BACKGROUND: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. METHODS: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). DISCUSSION: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02442375 .