Dataset Information

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base.

ABSTRACT:

Purpose

To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base.

Materials and methods

Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters.

Results

Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2-69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm³ volume receiving the maximum dose (D0.5cm³, D1cm³, and D2cm³, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm³ gave the highest AUC (0.935) among dose parameters. The 11-cm³ cutoff value for aV50 and 62 GyRBE for D2cm³ showed maximum specificity and sensitivity.

Conclusion

The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm³, D2cm³ ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

SUBMITTER: Kitpanit S

PROVIDER: S-EPMC7302730 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base.

Kitpanit Sarin S Lee Anna A Pitter Ken L KL Fan Dan D Chow James C H JCH Neal Brian B Han Zhiqiang Z Fox Pamela P Sine Kevin K Mah Dennis D Dunn Lara A LA Sherman Eric J EJ Michel Loren L Ganly Ian I Wong Richard J RJ Boyle Jay O JO Cohen Marc A MA Singh Bhuvanesh B Brennan Cameron W CW Gavrilovic Igor T IT Hatzoglou Vaios V O'Malley Bernard B Zakeri Kaveh K Yu Yao Y Chen Linda L Gelblum Daphna Y DY Kang Jung Julie JJ McBride Sean M SM Tsai Chiaojung J CJ Riaz Nadeem N Lee Nancy Y NY

International journal of particle therapy 20200528 4

<h4>Purpose</h4>To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base.<h4>Materials and methods</h4>Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 ...[more]

PMID: 32582816

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Project description:BackgroundTemporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk estimates of TLN after Intensity-Modulated Proton Therapy for HNC.Material and methodsSeventy-five temporal lobes from 45 previously treated patients were included in the analysis. Sixteen temporal lobes had radiation associated Magnetic Resonance image changes (TLIC) suspected to be early signs of TLN. Fixed (RWDFix) and variable RBE-weighed doses (RWDVar) were calculated using RBE = 1.1 and two RBE models, respectively. RWDFix and RWDVar for temporal lobes were compared using Friedman's test. Based on RWDFix, six NTCP models were fitted and internally validated through bootstrapping. Estimated probabilities from RWDFix and RWDVar were compared using paired Wilcoxon test. Seven dose constraints were evaluated separately for RWDFix and RWDVar by calculating the observed proportion of TLIC in temporal lobes meeting the specific dose constraints.ResultsRWDVar were significantly higher than RWDFix (p < 0.01). NTCP model performance was good (AUC:0.79-0.84). The median difference in estimated probability between RWDFix and RWDVar ranged between 5.3% and 20.0% points (p < 0.01), with V60GyRBE and DMax at the smallest and largest differences, respectively. The proportion of TLIC was higher for RWDFix (4.0%-13.1%) versus RWDVar (1.3%-5.3%). For V65GyRBE ≤ 0.03 cc the proportion of TLIC was less than 5% for both RWDFix and RWDVar.ConclusionNTCP estimates were significantly influenced by RBE variations. Dmax as model predictor resulted in the largest deviations in risk estimates between RWDFix and RWDVar. V65GyRBE ≤ 0.03 cc was the most consistent dose constraint for RWDFix and RWDVar.

Project description:BackgroundTo investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods.MethodsWe retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC.ResultsCompared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70).ConclusionOur study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Project description:Background Skull base chordoma and chondrosarcoma are exceptionally rare bone tumors with high propensity for local recurrence. Different postoperative radiation modalities are often used to improve the clinical efficacy. Proton therapy (PT) might be among the most promising ones because of the unique ballistic characteristics of high-energy particles. However, previous meta-analysis often included studies with combined radiation techniques. No systematic review to date has directly analyzed the survival and toxicity of pure PT for these two types of malignancies. Methods By following the PRISMA guidelines, a systematic search of three databases was conducted. Articles were screened and data were extracted according to a prespecified scheme. R 4.2.0 software was used to conduct the meta-analysis. Normal distribution test was used for the incidence rate of each subgroup. Results A total of seven studies involving 478 patients were included in this analysis. The quality of included articles ranged from moderate to high quality. All patients were histopathologically diagnosed with chordoma or chondrosarcoma, and the follow-up time of the cohort ranged from 21 to 61.7 months. For PT planning, the median target volume ranged from 15 cc to 40 cc, and the administered median dose varied from 63 to 78.4 GyRBE at 1.8–2.0 GyRBE per fraction. The 1-, 2-, 3-, 5-, and 7-year local control and overall survival rates were 100%, 93%, 87%, 78%, and 68%, and 100%, 99%, 89%, 85%, and 68%, respectively. The late grade 3 or higher toxicities were reported in only two involved articles. Conclusions Until now, medical centers worldwide have exerted PT to improve outcomes of skull base chordomas and chondrosarcomas. PT not combined with other radiation modalities showed favorable local control and survival with a low incidence of severe radiation-induced toxicities, which manifests promising clinical benefits. However, high-quality evidence is still limited, requiring future clinical trials and prospective studies in selected patients.

Project description:ImportanceUse of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret.ObjectiveTo evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma.Design, setting, and participantsThis retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects.ExposuresProton therapy reirradiation.Main outcomes and measuresFollow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS.ResultsA total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P < .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects.Conclusions and relevanceThe findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Dataset Information

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base.

Purpose

Materials and methods

Results

Conclusion

Publications

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base.

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