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

BACKGROUND AND PURPOSE: Primary radiotherapy is often preferred for early-stage cancer of the nasal vestibule (CNV), combining high disease control with preservation of nasal anatomy. However, due to practice variation and an absence of comparative trials, no consensus exists on preference for brachytherapy (BT) or external beam radiotherapy (EBRT). We compared these modalities in terms of disease control, nose preservation rates and toxicity. MATERIALS AND METHODS: Medical records of 225 patients with T1-T2 squamous cell carcinoma of the nasal vestibule treated with 3D image-guided primary radiotherapy between Jan 2010 and Dec 2016 in 6 Dutch institutions were reviewed retrospectively. RESULTS: 153 of 225 patients were treated with BT, 65 with EBRT and 7 with other modalities. Median follow-up was 46 months. Overall 3-year local control (LC) and regional control (RC) were 87% and 89%. Five-year disease-specific survival (DSS) and overall survival (OS) were 94% and 82%. Three-year survival with preserved nose (SPN) was 76%. BT provided higher 3-year LC (95% vs 71%, p < 0.01) and SPN compared with EBRT (82% vs 61%, p < 0.01). Multivariable and propensity-score-matched cohort analyses confirmed better outcomes after BT. No difference was seen in DSS or OS. Five-year incidence of CTCAE 5.0 grade ≥2 toxicity was higher after BT (20% vs 3%, p = 0.03) and consisted mostly of radiation ulcers. 50% of all late toxicity recovered. CONCLUSION: In this largest-to-date multicenter analysis of T1-T2 CNV, BT achieved superior LC and SPN compared with EBRT. Grade 1-2 radiation ulcers occurred more frequently after brachytherapy, but were transient in half the cases. Considering these results, BT can be recommended as first-line treatment for T1-T2 CNV.

Merkel Cell Carcinoma: New Trends.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin mainly seen in the elderly. Its incidence is rising due to ageing of the population, increased sun exposure, and the use of immunosuppressive medication. Additionally, with the availability of specific immunohistochemical markers, MCC is easier to recognize. Typically, these tumors are rapidly progressive and behave aggressively, emphasizing the need for early detection and prompt diagnostic work-up and start of treatment. In this review, the tumor biology and immunology, current diagnostic and treatment modalities, as well as new and combined therapies for MCC, are discussed. MCC is a very immunogenic tumor which offers good prospects for immunotherapy. Given its rarity, the aggressiveness, and the frail patient population it concerns, MCC should be managed in close collaboration with an experienced multidisciplinary team.

18F-FDG-PET/CT-based treatment planning for definitive (chemo)radiotherapy in patients with head and neck squamous cell carcinoma improves regional control and survival.

BACKGROUND AND PURPOSE: Multimodality imaging including 18F-FDG-PET has improved the detection threshold of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The aim of this retrospective analysis is to investigate the impact of FDG-PET/CT-based nodal target volume definition (FDG-PET/CT-based NTV) on radiotherapy outcomes, compared to conventional CT-based nodal target volume definition (CT-based NTV). MATERIALS AND METHODS: Six-hundred-thirty-three patients treated for HNSCC with definitive (chemo)radiotherapy using IMRT/VMAT techniques between 2008 and 2017 were analyzed. FDG-PET/CT-based NTV was performed in 46% of the patients. The median follow-up was 31 months. Diagnostic imaging depicting the regional recurrence was co-registered with the initial CT-scan to reconstruct the exact site of the recurrence. Multivariate Cox regression analysis was performed to identify variables associated with radiotherapy outcome. RESULTS: FDG-PET/CT-based NTV improved control of disease in the CTVelective-nodal (HR: 0.33, p = 0.026), overall regional control (HR: 0.62, p = 0.027) and overall survival (HR: 0.71, p = 0.033) compared to CT-based NTV. The risk for recurrence in the CTVelective-nodal was increased in case of synchronous local recurrence of the primary tumor (HR: 12.4, p < 0.001). CONCLUSION: FDG-PET/CT-based NTV significantly improved control of disease in the CTVelective-nodal, overall regional control and overall survival compared to CT-based NTV. A significant proportion of CTVelective-nodal recurrences are potentially new nodal manifestations from a synchronous local recurrent primary tumor. These results support the concept of target volume transformation and give an indication of the potential of FDG-PET to guide gradual radiotherapy dose de-escalation in elective neck treatment in HNSCC.

Image Guided Brachytherapy for Cancer of the Nasal Vestibule: Local Control and Cosmesis.

PURPOSE: To evaluate the efficacy of modern image guided brachytherapy for squamous cell carcinoma of the nasal vestibule, to explore tumor volume as a prognostic factor for local and regional recurrence, and to assess patient satisfaction with nasal function and appearance after treatment. METHODS AND MATERIALS: In a retrospective analysis, we reviewed the medical records of 102 patients with Wang T1-T2 nasal vestibule cancer treated at a single institution with brachytherapy as the sole treatment. Median follow-up time was 42 months (range, 3-210 months). A patient satisfaction study using the validated Nasal Appearance and Function Evaluation Questionnaire was conducted among 42 patients more than 1 year after treatment. A statistically significant cutoff point for tumor volume as a prognostic factor of local control was established using Youden's index method. RESULTS: Seventy-seven of 102 patients were treated with interstitial implants, and 25 patients were treated by an intracavitary mould technique. The 5-year control rates were 95%, 91%, and 83% for local, regional, and locoregional control, respectively. Tumor volume ≥2.3 cm3 resulted in worse 3-year regional control compared to tumor volume <2.3 cm3 (62% vs 96%; P = .01). Ultimate regional control after salvage treatment was 96%, with no significant difference observed between subgroups by tumor volume (92% for ≥2.3 cm3 vs 96% for <2.3 cm3; P = .57). Three patients with regional failure developed distant metastases. Five-year disease-specific survival and overall survival were 94% and 74%, respectively. Patient-assessed cosmetic and functional satisfaction were both rated high (mean 3.7 and 4.0 of 5, respectively). CONCLUSION: We report the largest cohort to date treated with brachytherapy as the sole treatment for nasal vestibule carcinoma. Brachytherapy offers excellent local control for Wang T1-T2 tumors with high patient satisfaction. Tumor volume is an adequate predictive factor for patients at risk of regional recurrence, but ultimate control rates after salvage treatment are high. Therefore, we do not recommend elective treatment of the neck.

Reirradiation of head and neck cancer: Long-term disease control and toxicity.

BACKGROUND: The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. METHODS: We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. CONCLUSION: Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017.

Patterns of Recurrence in Electively Irradiated Lymph Node Regions After Definitive Accelerated Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma.

PURPOSE: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer. METHODS AND MATERIALS: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated. The exact sites of regional recurrences were reconstructed and projected on the initial radiation therapy planning CT scan by performing coregistration with diagnostic imaging of the recurrence. RESULTS: The actuarial rate of recurrence in electively irradiated lymph node regions at 2 years was 5.1% (95% confidence interval 2.4%-7.8%). Volumetric analysis showed an increased risk of recurrence with increasing nodal volume. Receiver operating characteristic analysis demonstrated that the summed long- and short-axis diameter is a good alternative for laborious volume calculations, using ≥17 mm as cut-off (hazard ratio 17.8; 95% confidence interval 5.7-55.1; P<.001). CONCLUSIONS: An important risk factor was identified that can help clinicians in the pretreatment risk assessment of borderline-sized lymph nodes. Not overtly pathologic nodes with a summed diameter ≥17 mm may require a higher than elective radiation therapy dose. For low-risk elective regions (all nodes <17 mm), the safety of dose de-escalation below the traditional 45 to 50 Gy should be investigated.

Stereotactic body radiotherapy: a promising treatment option for the boost of oropharyngeal cancers not suitable for brachytherapy: a single-institutional experience.

PURPOSE: To prospectively assess the outcome and toxicity of frameless stereotactic body radiotherapy (SBRT) as a treatment option for boosting primary oropharyngeal cancers (OPC) in patients who not suitable for the standard brachytherapy boost (BTB). METHODS AND MATERIALS: Between 2005 and 2010, 51 patients with Stage I to IV biopsy-proven OPC who were not suitable for BTB received boosts by means of SBRT (3 times 5.5 Gy, prescribed to the 80% isodose line), after 46 Gy of IMRT to the primary tumor and neck (when indicated). Endpoints of the study were local control (LC), disease-free survival (DFS), overall survival (OS), and acute and late toxicity. RESULTS: After a median follow-up of 18 months (range, 6-65 months), the 2-year actuarial rates of LC, DFS, and OS were 86%, 80%, and 82%, respectively, and the 3-year rates were 70%, 66%, and 54%, respectively. The treatment was well tolerated, as there were no treatment breaks and no Grade 4 or 5 toxicity reported, either acute or chronic. The overall 2-year cumulative incidence of Grade ≥2 late toxicity was 28%. Of the patients with 2 years with no evidence of disease (n = 20), only 1 patient was still feeding tube dependent and 2 patients had Grade 3 xerostomia. CONCLUSIONS: According to our knowledge, this study is the first report of patients with primary OPC who received boosts by means of SBRT. Patients with OPC who are not suitable for the standard BTB can safely and effectively receive boosts by SBRT. With this radiation technique, an excellent outcome was achieved. Furthermore, the SBRT boost did not have a negative impact regarding acute and late side effects.