Treatment-related hearing loss in weekly versus triweekly cisplatin chemoradiation for head and neck cancer.

PURPOSE: Cisplatin-induced hearing loss is a common side effect in patients treated with cisplatin-based chemoradiation (CRT) for head and neck squamous cell carcinoma. The extent of hearing loss after concurrent CRT was compared between triweekly (3 × 100 mg/m2) and weekly (7 × 40 mg/m2) cisplatin CRT. METHOD: This retrospective cohort study was conducted in the Antoni van Leeuwenhoek Hospital and included 129 patients with cisplatin-based CRT for head and neck cancer (72 treated in the triweekly and 57 in the weekly regimen). Baseline and follow-up pure tone audiometry was conducted to assess hearing loss. Clinically relevant hearing loss was defined as a decline upon treatment of ≥ 10 decibel at a pure tone average 1-2-4 kHz and/or 8-10-12.5 kHz. RESULTS: The incidence of clinically relevant cisplatin CRT induced hearing loss was 42% in the triweekly versus 19% in the weekly group (p < 0.01). The mean threshold shift at a pure tone average (PTA) 1-2-4 kHz was 9.0 decibel in the triweekly compared to 4.3 decibel in the weekly CRT group (p < 0.01). At PTA 8-10-12.5 kHz, the incidence of clinically relevant hearing loss was 75% in the triweekly compared to 74% in the weekly CRT group (p = 0.87). The mean threshold shift at PTA 8-10-12.5 kHz was 20.2 decibel versus 15.6 decibel, respectively (p = 0.07). CONCLUSION: Cisplatin-dose reduction to a weekly cisplatin CRT regimen for head and neck cancer may reduce the incidence of clinically relevant hearing loss at frequencies vital for speech perception.

Local control and toxicity after stereotactic radiotherapy in brain metastases patients and the impact of novel systemic treatments.

BACKGROUND AND PURPOSE: Treatment modalities for patients with brain metastases consist of surgery, radiotherapy, and systemic treatments such as immunotherapy and targeted therapy. Although much is known about local control of brain metastases after radiotherapy and surgery alone, more understanding is needed of the additional effect of new systemic treatments. Our study presents real-world data about the combined effects of different local and systemic treatment strategies on local response of irradiated brain metastases. MATERIALS AND METHODS: We performed a retrospective consecutive cohort study of patients that presented with brain metastases in our institution between June 2018 and May 2020, reporting the impact of radiotherapy alone versus radiotherapy combined with systemic treatment on local control of irradiated brain metastases and toxicity. Chemotherapy and targeted therapy were temporarily discontinued around irradiation. RESULTS: 262 consecutively treated patients were included in the study. Median time to local failure of irradiated brain metastases was 18 months (IQR 9-34), median overall survival was 20 months (IQR 10-36). 211 (81 %) patients received systemic treatment. Patients with breast cancer had a worse local control (HR 2.3, 95 % CI 1.0-5.0, p = 0.038), as did patients without any systemic treatment (HR 2.1, 95 % CI 1.1-4.3, p = 0.034). Symptomatic radiation necrosis occurred in 36 (14 %) patients. A diameter > 2.5 cm was associated with a higher risk of radiation necrosis. No association was found between systemic treatment in combination with local radiotherapy and symptomatic radiation necrosis. CONCLUSION: Patients who received any form of systemic treatment had better local control after stereotactic radiosurgery for brain metastases. We did not find an association between systemic treatment and the incidence of radiation necrosis.

From reactive to proactive tube feeding during chemoradiotherapy for head and neck cancer: A clinical prediction model-based approach.

OBJECTIVES: Feeding tubes are placed unnecessarily in a proportion of head and neck cancer (HNC) patients treated with chemoradiotherapy (CRT) when prophylactic tube placement protocols are used. This may have a negative impact on the risk of long-term dysphagia. Reactive tube placement protocols, on the other hand, might result in weight loss and treatment interruption. The objective of this study is to identify patients at risk for prolonged tube dependency in order to implement a personalized strategy regarding proactive tube placement. MATERIALS AND METHODS: A retrospective study was performed in a consecutive cohort of HNC patients treated with primary CRT for whom a reactive tube placement protocol was used. A prediction model was developed to predict prolonged (> 90 days) feeding tube dependency. Model performance and clinical net benefit of the model were assessed. RESULTS: Of the 336 included patients, 229 (68%) needed a feeding tube during CRT and 151 (45%) were prolonged feeding tube dependent. The prediction model includes the predictors pretreatment BMI, weight loss, Functional Oral Intake Scale and T-stage. Discriminatory ability is fair (area under the ROC-curve of 0.69) and calibration is adequate (Hosmer and Lemeshow test p = .254). The model shows net benefit over current practice for probability thresholds from 35 to 80%. CONCLUSION: The developed model can be used to select patients for proactive feeding tube placement during primary CRT for HNC. The nomogram with easily obtainable parameters is a useful tool for clinicians to support shared decision making regarding proactive tube placement.

The impact of cumulative dose of cisplatin on outcome of patients with head and neck squamous cell carcinoma.

Despite the wide use of cisplatin-based concomitant chemoradiotherapy (CCRT) for head and neck squamous cell carcinoma (HNSCC), data on the optimal regimen and cumulative dose are scarce and frequently conflicting. We aimed to evaluate the compliance and the impact of the cumulative dose of cisplatin on overall survival (OS), disease-free survival (DFS), loco-regional control (LRC), and distant-metastasis-free survival (DMFS) in a retrospective study. Between 2008 and 2015, 279 patients with HNSCC scheduled for CCRT (three courses of 3-week 100 mg/m2 cisplatin) were identified. Of the whole group, 14% did not receive any cisplatin and 26% received daily cisplatin. In patients planned for three courses (n = 167), 56% received 3, 20% received 2, and 24% received one course. After median follow-up of 31.6 months, the actuarial OS, DFS, LRC, and DMFS rates at 3 years for patients received cumulative dose of ≥200 mg/m2 were significantly better compared to those received <200 mg/m2; 74 vs. 51% for OS, 73 vs. 49% for DFS, 80 vs. 58% for LRC (p < 0.001), and 85 vs. 76% for DMFS (p = 0.034). At multivariate analysis, the cumulative cisplatin dose (≥200 vs. <200 mg/m2) was significantly predictive for OS (HR 2.05; 95% CI 1.35-3.13, p = <0.001). Borderline GFR (60-70 mL/min) at baseline predicts compliance for ≥two courses (p = 0.003). In conclusion, considerable proportion of patients did not receive all pre-planned courses of cisplatin. Patients receiving cumulative cisplatin dose ≥200 mg/m2 had significantly better outcome than those receiving <200 mg/m2 and cumulative dose <200 mg/m2 might even be detrimental. These findings increased the bulk of slowly growing evidence on the optimal cumulative dose of cisplatin. Baseline GFR might predict compliance.

Recurrent oropharyngeal cancer after organ preserving treatment: pattern of failure and survival.

The objectives is to thoroughly analyze the pattern of failure and oncologic outcome in recurrent oropharyngeal cancer (OPC) after (chemo)radiotherapy and correlate the site of failure to the planned radiation dose. Between January 2010 and April 2014, 57 patients with recurrent OPC after (chemo)radiotherapy were analyzed. Endpoints were pattern of failure and overall survival (OS). Local (LF) and regional failure (RF) were classified as in-field [>50% within gross tumor volume (GTV)], marginal [<50% within GTV but >50% within clinical target volume (CTV)], or out-of-field (>50% outside CTV) recurrences. In the whole group, 70 recurrences were reported. Of the 31 LF, 29 (93.5%) were in-field and 2 (6.5%) were marginal. No out-field LF was reported. Of the 21 RF, 13 RF (62%) were in-field, 6 (28.5%) marginal, and 2 (9.5%) out-of-field recurrences. Forty-three percent of RF was developed in an electively treated neck level, and 2 of them were contralateral. OS at 2 years in recurrent HPV positive, compared to HPV-negative OPC, were 66 and 18%, respectively (p = 0.011). OS was also significantly better in patients that were salvage treatment which was possible (70 vs. 6%, p < 0.001). Median survival after distant failure was 3.6 months. The great majority of LFs were located within the GTV and 43% of RFs developed in an electively treated neck level. The currently used margins and dose recipe and the indication for bilateral nodal irradiation need to be reevaluated. OS was significantly better in recurrent HPV-positive OPC and in patients, where salvage treatment was possible.

The influence of nodal yield in neck dissections on lymph node ratio in head and neck cancer.

OBJECTIVES: Recent studies suggest that lymph node ratio (LNR) is a strong prognostic factor in head and neck cancer. This study aims to determine if the yield of harvested lymph nodes (LNs) influences the LNR. METHODS: The study included 522 head and neck cancer patients, undergoing 638 primary and salvage (selective) neck dissections between 2002 and 2012. Before 2007 the neck dissection specimens were macroscopically and microscopically examined by pathologists and after 2007 the macroscopic examination was performed by pathology technicians. For comparison of mean LN yields, univariate and multivariate analyses were performed. RESULTS: The mean number of LNs among 374 specimens examined by pathologists was 24 (range 0-89) vs. 32 (range 2-89) among 264 specimens examined by pathology technicians (P<.001). This caused the mean LNR in the non pre-treated patient group to drop from 11.4% to 8.7%. The counts of LNs per type of neck dissection were significantly different and increased with the number of levels involved. However, there was no linear relationship and the higher yields could be mostly ascribed to LNs in level V. The LNR varied from 8.1% to 18.4% among the different types of neck dissections. CONCLUSIONS: A significant increase in the number of harvested LNs, but a decrease in LNR was observed after introducing pathology technicians for macroscopic examination. A clear association between the extent of the dissection and the number of harvested LNs was observed. LNR appears to be strongly dependent on the harvesting protocol and the extent of the dissection.