The Dynamics of Dose Escalation of Radiotherapy for Localized Prostate Cancer

It is a well-known fact that there is a dose-response relationship for clinical control of localized prostate cancer. As a result of the promising high local control rates observed in different prospective dose-escalation studies in the USA, the CKVO 96-10 study was initiated in four cancer institutes in The Netherlands in 1997 investigating the tumor control and toxicity as a consequence of dose-escalation, comparing the standard dose of 68 Gy with the experimental dose of 78 Gy. • The benefit of dose-escalation of RT for localized prostate cancer in terms of local control is undisputed. • Patients with intermediate-risk prostate cancer and those with iPSA between 8 and 18 ug/L seem to benefit most from high-dose RT. However, from the current knowledge, neither low-risk nor high-risk patients could be safely excluded from high-dose RT because of the negative test of heterogeneity. Randomized trials are warranted to answer this important issue. • The associated increased GI toxicity would be reduced by the recent implementation of image-guide intensity-modulated radiotherapy at our institute. • Despite the increased GI toxicity seen in patients treated in the high-dose arm, dose-escalation did not appear to decrease QoL-scores significantly in these patients. • Predictive models need to be developed in order to identify patients at high risk of toxicity from high-dose RT. The possible risks of complications and deterioration of QoL-scores must be carefully weighted against the benefit from dose-escalation. • The optimal combination of HT and RT in high-risk prostate cancer patients are not yet well-defined

Radiotherapy as nose preservation treatment strategy for cancer of the nasal vestibule:the Dutch experience

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SPECT/CT-guided lymph drainage mapping for the planning of unilateral elective nodal irradiation in head and neck squamous cell carcinoma

To investigate the feasibility of lymph drainage mapping (LDM) using SPECT/CT to help select head and neck cancer (HNSCC) patients for unilateral elective neck irradiation (ENI). Patients with lateralized HNSCC treated with radiotherapy routinely undergo bilateral ENI, despite the incidence of contralateral regional failure being relatively low even after unilateral ENI. We hypothesized that patients with a lateralized tumor without visible lymph drainage to the contralateral neck have an extremely low risk of contralateral involved nodes. Excluding the contralateral neck from elective irradiation will reduce radiation-induced toxicity and improve quality-of-life.Fifty-five patients with lateralized cT1-3N0-2bM0 HNSCC not crossing the midline underwent LDM. Radiolabeled Tc-99m-nanocolloid was injected in 4-5 depots around and in the primary tumor. Lymph drainage patterns were visualized using planar scintigraphy and SPECT/CT after 4 h. We report on the incidence of contralateral drainage, the location of draining areas, and the size of underlying nodes.Lymphatic drainage was successfully visualized in 54 patients (98%). In 11 patients (20%) with visible contralateral drainage, 14 draining areas (16 nodes; median volume 0.50 cc, diameter 8.0 mm) were identified. Neck levels with contralateral drainage were level II (88%), III (25%), and IV (13%). Contralateral drainage was significantly higher in T3 compared to T1-2 tumors (45 and 14%, respectively, P = 0.035).SPECT/CT-guided LDM is feasible and can be used to guide unilateral ENI in HNSCC patients in prospective studies. In addition, the anatomical confidence in visualization of contralateral drainage indicates a potential for ENI limited to draining levels alone.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Incidence of contralateral regional failure in the electively irradiated contralateral neck of patients with head and neck squamous cell carcinoma

Background: The vast majority of patients with head and neck squamous cell carcinoma (HNSCC) routinely undergo elective nodal irradiation (ENI) to both sides of the neck. Little is known about the extent to which bilateral ENI prevents regional failure (RF) and contralateral RF (cRF) in particular, while such knowledge is necessary to evaluate the results of more selective approaches like unilateral ENI. We investigated the rate and pattern of RF after bilateral ENI, the rate of cRF in the electively irradiated contralateral neck, and tried to identify risk factors for development of cRF.Materials and methods: Retrospective cohort study of a consecutive series of 605 patients with T1-4N0-3 HNSCC treated between 2008 and 2017 with primary (chemo) radiation and bilateral ENI.Results: Median follow-up was 43 months (range 1.4-126). Three-year cumulative incidence of RF was 12.7%. Three-year cumulative incidences of ipsilateral RF (iRF) and cRF were 10.6% and 2.8%, respectively. All cRF occurred within the electively treated volume. Salvage treatment was possible in 65% and 59% of patients with iRF and cRF, respectively (p = 0.746). The 3-year overall survival rates after RF in patients with iRF and cRF were 27.4% and 41.2%, respectively (p = 0.713). Three-year cancer-specific survival rates were 31.6% and 48.1%, respectively (p = 0.634). In multivariate analysis, no significant predictive factors were identified for cRF after bilateral ENI.Conclusion: Contralateral regional failure is rare, but still occurs in 2.8% of patients treated with bilateral ENI. The possibilities for salvage treatment, the rates of overall survival and cancer-specific survival were comparable to patients with iRF. (C) 2019 The Author(s). Published by Elsevier B.V.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Dysphagia, trismus and speech impairment following radiation-based treatment for advanced stage oropharyngeal carcinoma: a one-year prospective evaluation

OBJECTIVE: The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III-IV oropharyngeal carcinoma (OPC). METHODS: Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists . RESULTS: Objective and patient-perceived function deteriorated until 6 months and improved until 12 months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low. CONCLUSION: Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies

IMRT for image-guided single vocal cord irradiation

Purpose: We have been developing an image-guided single vocal cord irradiation technique to treat patients with stage T1a glottic carcinoma. In the present study, we compared the dose coverage to the affected vocal cord and the dose delivered to the organs at risk using conventional, intensity-modulated radiotherapy (IMRT) coplanar, and IMRT non-coplanar techniques. Methods and Materials: For 10 patients, conventional treatment plans using two laterally opposed wedged 6-MV photon beams were calculated in XiO (Elekta-CMS treatment planning system). An in-house IMRT/beam angle optimization algorithm was used to obtain the coplanar and non-coplanar optimized beam angles. Using these angles, the IMRT plans were generated in Monaco (IMRT treatment planning system, Elekta-CMS) with the implemented Monte Carlo dose calculation algorithm. The organs at risk included the contralateral vocal cord, arytenoids, swallowing muscles, carotid arteries, and spinal cord. The prescription dose was 66 Gy in 33 fractions. Results: For the conventional plans and coplanar and non-coplanar IMRT plans, the population-averaged mean dose ± standard deviation to the planning target volume was 67 ± 1 Gy. The contralateral vocal cord dose was reduced from 66 ± 1 Gy in the conventional plans to 39 ± 8 Gy and 36 ± 6 Gy in the coplanar and non-coplanar IMRT plans, respectively. IMRT consistently reduced the doses to the other organs at risk. Conclusions: Single vocal cord irradiation with IMRT resulted in good target coverage and provided significant sparing of the critical structures. This has the potential to improve the quality-of-life outcomes after RT and maintain the same local control rates

Combined-modality treatment improved outcome in sinonasal undifferentiated carcinoma: Single-institutional experience of 21 patients and review of the literature

The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains unclear. We report our results on the outcome and toxicity of patients with SNUC treated by a combined modality and attempt to define the optimal treatment strategies by reviewing the literature. Between 1996 and 2010, 21 consecutive patients with SNUC were treated by any combination of surgery, chemotherapy and radiotherapy. End points were local control (LC), regional control (RC), disease-free (DFS), cause-specific (CSS) overall survival (OS), and late toxicity. Organ preservation was defined as visual preservation without orbital exenteration. After median follow-up of 54 months, the 5-year actuarial rates of LC, RC, DFS, CSS, and OS were 80, 90, 64, 74, and 74 % respectively. On multivariate analysis, T-stage and multimodality treatment approach correlated significantly with LC. Elective nodal irradiation was given to 42 % of high-risk node-negative patients. None of them developed regional failure. The overall 5-year incidence of grade ≥2 late toxicity was 30 %. Treatment-related blindness was significantly decreased in patients treated with intensity-modulated radiotherapy (IMRT), compared to 2D and 3D-conformal radiotherapy (3DCRT), with organ preservation rates of 86 and 14 % respectively (p = 0.006). We concluded that combined-modality treatment with three, or at least two, modalities resulted in good LC, but with high overall rate of late toxicity. However, the incidence of late toxicity and permanent visual impairment were decreased over time by the introduction of IMRT. Because of the improvement in therapeutic ratio achieved by using IMRT, this highly conformal radiation technique should be the standard of care in patients with SNUC

SPECT/CT-guided elective nodal irradiation for head and neck cancer: Estimation of clinical benefits using NTCP models

Background and purpose: The great majority of patients with lateralized head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy routinely undergo bilateral elective nodal irradiation (ENI), even though the incidence of contralateral regional failure after unilateral ENI is low. Excluding the contralateral neck from elective irradiation could reduce radiation-related toxicity and improve quality-of-life. The current study investigated the dosimetric benefits of a novel approach using lymph drainage mapping by SPECT/CT to select patients for unilateral ENI.Patients and methods: Forty patients with lateralized cT1-3N0-2bM0 HNSCC underwent lymph drainage mapping. Two radiation plans were made; the real plan with which patients were actually treated (selective SPECT/CT-guided plan irradiating the ipsilateral neck any contralateral draining level); and the virtual plan (standard plan according to institutional guidelines, as if the same patient would have been treated bilaterally). Radiation doses to clinically important organs-at-risk were compared between the two plans. We used five normal tissue complication probability (NTCP) models to predict the clinical benefits of this approach.Results: Median dose reductions to the contralateral parotid gland, contralateral submandibular gland, glottic larynx, supraglottic larynx, constrictor muscle and thyroid gland were 19.2, 27.3, 11.4, 9.7, 12.1 and 18.4 Gy, respectively. Median NTCP reductions for xerostomia, contralateral parotid function, dysphagia, hypothyroidism and laryngeal edema were 20%, 14%, 10%, 20% and 5% respectively.Conclusions: Selective SPECT/CT-guided ENI results in significant dose reductions to various organs-at risk and corresponding NTCP values, and will subsequently reduce the incidence and severity of different troublesome radiation-related toxicities and improve quality-of-life. (C) 2018 Elsevier B.V. All rights reserved.Biological, physical and clinical aspects of cancer treatment with ionising radiatio