National Protocol for Model-Based Selection for Proton Therapy in Head and Neck Cancer.
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ABSTRACT:
SUBMITTER: Langendijk JA
PROVIDER: S-EPMC8270079 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT).This prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve.192 patients were included. The most prevalent tumor site was oropharynx (n=86, 45%), followed by sinonasal (n=28), nasopharyngeal (n=27) or parotid (n=27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6months after PBT; 0.70 versus 0.68 for dry mouth 6months after PBT; and 0.73 versus 0.85 for hypothyroidism 12months after PBT.Although a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC.
| S-EPMC5474306 | biostudies-literature
Project description:Cancer-related financial toxicity impacts head and neck cancer patients and survivors. With increasing use of proton therapy as a curative treatment for head and neck cancer, the multifaceted financial and economic implications of proton therapy-dimensions of "financial toxicity"-need to be addressed. Herein, we identify knowledge gaps and potential solutions related to the problem of financial toxicity. To date, while cost-effectiveness analysis has been used to assess the value of proton therapy for head and neck cancer, it may not fully incorporate empiric comparisons of patients' and survivors' lost productivity and disability after treatment. A cost-of-illness framework for evaluation could address this gap, thereby more comprehensively identifying the value of proton therapy and distinctly incorporating a measurable aspect of financial toxicity in evaluation. Overall, financial toxicity burdens remain understudied in head and neck cancer patients from a patient-centered perspective. Systematic, validated, and accurate measurement of financial toxicity in patients receiving proton therapy is needed, especially relative to conventional photon-based strategies. This will enrich the evidence base for optimal selection and rationale for payer coverage of available treatment options for head and neck cancer patients. In the setting of cancer care delivery, a combination of conducting proactive screening for financial toxicity in patients selected for proton therapy, initiating early financial navigation in vulnerable patients, engaging stakeholders, improving oncology provider team cost communication, expanding policies to promote price transparency, and expanding insurance coverage for proton therapy are critical practices to mitigate financial toxicity in head and neck cancer patients.
| S-EPMC8270089 | biostudies-literature
Project description:PurposeTo characterize our experience and the disease control and toxicity of proton therapy (PT) for patients with head and neck cancer (HNC).Patients and methodsClinical outcomes for patients with HNC treated with PT at our institution were prospectively collected in 2 institutional review board-approved prospective studies. Descriptive statistics were used to summarize patient characteristics and outcomes. Overall survival, local-regional control, and disease-free survival were estimated by the Kaplan-Meier method. Treatment-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03) scale.ResultsThe cohort consisted of 573 patients treated from February 2006 to June 2018. Median patient age was 61 years. Oropharynx (33.3%; n = 191), paranasal sinus (11%; n = 63), and periorbital tissues (11%; n = 62) were the most common primary sites. Patients with T3/T4 or recurrent disease comprised 46% (n = 262) of the cohort. The intent of PT was definitive in 53% (n = 303), postoperative in 37% (n = 211), and reirradiation in 10% (n = 59). Median dose was 66 Gy (radiobiological equivalent). Regarding systemic therapy, 43% had received concurrent (n = 244), 3% induction (n = 19), and 15% (n = 86) had both. At a median follow-up of 2.4 years, 88 patients (15%) had died and 127 (22%) developed disease recurrence. The overall survival, local-regional control, and disease-free survival at 2 and 5 years were, respectively, 87% and 75%, 87% and 78%, and 74% and 63%. Maximum toxicity (acute or late) was grade 3 in 293 patients (51%), grade 2 in 234 patients (41%), and grade 1 in 31 patients (5%). There were 381 acute grade 3 and 190 late grade 3 unique toxicities across 212 (37%) and 150 (26%) patients, respectively. There were 3 late-grade 4 events across 2 patients (0.3%), 2 (0.3%) acute-grade 5, and no (0%) late-grade 5 events.ConclusionsThe overall results from this prospective study of our initial decade of experience with PT for HNC show favorable disease control and toxicity outcomes in a multidisease-site cohort and provide a reference benchmark for future comparison and study.
| S-EPMC8270083 | biostudies-literature
Project description:Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as "pencil beam proton therapy," is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.
| S-EPMC6615027 | biostudies-literature
Project description:ImportanceProton radiation therapy (PRT) has reduced radiation-induced toxic effects, such as mucositis and xerostomia, over conventional photon radiation therapy, leading to significantly improved quality of life in patients with head and neck cancers. However, the prevalence of osteoradionecrosis (ORN) of the jaw following PRT in these patients is less clear.ObjectiveTo report the prevalence and clinical characteristics of ORN in patients with oral and oropharyngeal cancer (OOPC) treated with PRT.Design, setting, and participantsThis case series reports a single-institution experience (Memorial Sloan Kettering Cancer Center, New York, New York) between November 2013 and September 2019 and included 122 radiation therapy-naive patients with OOPC treated with PRT. Data were analyzed from 2013 to 2019.Main outcomes and measuresClinical parameters, including sex, age, comorbidities, tumor histology, concurrent chemotherapy, smoking, comorbidities, and preradiation dental evaluation, were obtained from the medical record. Patients with clinical or radiographic signs of ORN were identified and graded using the adopted modified Glanzmann and Grätz grading system. Characteristics of ORN, such as location, clinical presentation, initial stage at diagnosis, etiology, time to diagnosis, management, and clinical outcome at the last follow-up, were also collected.ResultsOf the 122 patients (mean [SD] age, 63 [13] years; 45 [36.9%] women and 77 [63.1%] men) included in this study, 13 (10.6%) developed ORN following PRT during a median (range) follow-up time of 40.6 (<1-101) months. All patients had spontaneous development of ORN. At the time of initial diagnosis, grade 0, grade 1, grade 2, and grade 3 ORN were seen in 2, 1, 9, and 1 patient, respectively. The posterior ipsilateral mandible within the radiation field that received the full planned PRT dose was the most involved ORN site. At a median (range) follow-up of 13.5 (0.2-58.0) months from the time of ORN diagnosis, complete resolution, stable condition, and progression of ORN were seen in 3, 6, and 4 patients, respectively. The 3-year rates of ORN and death in the total cohort were 5.2% and 21.5%, while the 5-year rates of ORN and death were 11.5% and 34.4%, respectively.Conclusions and relevanceIn this case series, the prevalence of ORN following PRT was found to be 10.6%, indicating that ORN remains a clinical challenge even in the era of highly conformal PRT. Clinicians treating patients with OOPC with PRT should be mindful of this complication.
| S-EPMC9912132 | biostudies-literature
Project description:PurposeTo compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors.Methods and materialsFor 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT.ResultsThe robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0-21.1) and 8.1% (95% CI; 4.9-11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing.ConclusionsThe estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans.
| S-EPMC4816406 | biostudies-literature
Project description:PurposeTo 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 methodsMedical 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.ResultsBetween 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.ConclusionThe 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.
| S-EPMC7302730 | biostudies-literature
Project description:In spite of a rapidly expanding understanding of head and neck tumor biology and optimization of radiation, chemotherapy, and surgical treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer-related morbidity and mortality. Although our biologic understanding of these tumors had largely been limited to pathways driving proliferation, survival, and differentiation, the identification of HPV as a major driver of HNSCC and genomic sequencing analyses has dramatically influenced our understanding of tumor biology and approach to therapy. Here, we summarize molecular aspects of HNSCC biology and identify promising areas for potential diagnostic and therapeutic agents.
| S-EPMC4648693 | biostudies-other
Project description:BackgroundCurrently, in vivo model for personalised cancer drug testing is challenging. A zebrafish larvae xenograft model has been applied in recent years to cancer research, particularly for drug testing purposes, showing promising results in drug testing against patient-derived tumour xenografts. Currently, these xenograft models apply imaging techniques to measure drug efficacy. However, this method carries several limitations, including timely imaging, thereby reducing the available number of tested fish and drugs. Here, we propose a PCR-based fast assay to evaluate drug efficacy in a zebrafish larvae xenograft model.MethodsWe tested two primary and corresponding metastatic head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived tongue cancer sample applying zebrafish larvae xenograft model. Cisplatin efficacy was tested using imaging technique and compared the results with PCR-based methods. Drug screening of eight compounds was applied on both cell lines and patient sample using PCR.ResultsIn a head-to-head comparison, all the three techniques (imaging, quantitative PCR, and droplet digital PCR) showed similar reduction of the cancer cells growth after cisplatin treatment. Using the quantitative PCR assay, we demonstrated a dose-dependent response of HNSCC cells to cisplatin. Drug screening results of four HNSCC cell lines and patient sample revealed different drug efficacy between tested cancer cells.ConclusionWe introduce a novel, easy, fast and cost-effective PCR-based in vivo zebrafish larvae assay to test the response of cell lines and clinical tumour samples to anti-cancer drugs. This method goes hand-by-hand with the commonly used imaging assay.
| S-EPMC6647158 | biostudies-literature
Project description:Radiotherapy is a common treatment modality in the management of head and neck malignancies. In select clinical scenarios of well-lateralized tumors, radiotherapy can be delivered to the primary tumor or tumor bed and the ipsilateral nodal regions, while intentional irradiation of the contralateral neck is omitted. Proton beam therapy is an advanced radiotherapy modality that allows for the elimination of exit-dose through nontarget tissues such as the oral cavity. This dosimetric advantage is apt for unilateral treatments. By eliminating excess dose to midline and contralateral organs at risk and conforming dose around complex anatomy, proton beam therapy can reduce the risk of iatrogenic toxicities. Currently, there is no level I evidence comparing proton beam therapy to conventional photon radiation modalities for unilateral head and neck cancers. However, a growing body of retrospective and prospective evidence is now available describing the dosimetric and clinical advantages of proton beam therapy. Subsequently, the intent of this clinical review is to summarize the current evidence supporting the use of proton beam therapy in unilateral irradiation of head and neck cancers, including evaluation of disease site-specific evidence, unique challenging clinical scenarios, and ongoing clinical trials.
| S-EPMC8270109 | biostudies-literature