To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation ...(CCRT), against CCRT alone.
Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m(2), carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m(2) given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m(2)), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power.
Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% GCP vs 92.3% control; hazard ratio 1.05; 1-sided P=.494), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases-free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms.
Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.
Background
The efficacy of a combination of nimotuzumab, a humanized monoclonal antibody to the epidermal growth factor receptor, with chemoradiation in locally advanced head and neck squamous cell ...carcinoma (HNSCC) was evaluated in a phase II study.
Methods
Patients with stage III/IV HNSCC received 3‐weekly cisplatin 100 mg/m2 for three cycles and weekly nimotuzumab 200 mg for 8 weeks concurrently with radiotherapy. Primary endpoint was best overall response (BOR) and secondary endpoint was progression‐free survival (PFS).
Results
Thirty‐seven patients were included; the majority were Chinese (76%), male (89%), and had stage IVA/IVB HNSCC (92%). BOR of complete and partial response was seen in 22/37 (59%) and 10/37 (27%) patients, respectively. Median PFS was 17.5 months (95% CI: 11.1–54.5) and 3‐year PFS was 40.4% (95% CI: 24.3–55.9). The frequency and type of adverse events observed were similar to standard chemoradiation.
Conclusion
The combination of nimotuzumab with cisplatin and radiotherapy was safe and achieved high response rates in HNSCC.
Objectives/Hypothesis
Our study aimed to review the impact of preoperative radiotherapy (RT) and other factors on the lymph node count of neck dissection (ND) specimens from patients with head and ...neck cancer (HNC). A retrospective study was conducted on all patients with head and neck cancers who had undergone NDs in Singapore General Hospital between 1992 and 2013.
Study Design
Retrospective study.
Methods
Patients were categorized into two groups: patients treated with RT with or without chemotherapy before ND and patients who had undergone ND surgery without previous history of RT. The primary endpoint for this study would be the lymph node count from ND.
Results
The study cohort consists of 1,024 NDs on 829 patients. There were 597 (58.3%) radical/modified radical NDs involving levels I–V. Within this group, 75 (12.6%) NDs had preoperative RT. Preoperative RT and age were found to significantly reduce nodal yield in both univariate and multivariate analysis in the radical/modified radical ND subgroup. In our multivariate analysis, preoperative RT was shown to decrease the nodal yield by 7.464 (P = .0002, 95% confidence interval CI: −11.35 to −3.58). Advanced age independently decreases nodal yield, even after accounting for the effect of RT (P = .0002, 95% CI: −0.27 to −0.08). In addition, preoperative RT has a more pronounced effect in reducing lymph node count in the older age group.
Conclusions
Preoperative RT and advanced age are independent and synergistic factors that reduce nodal count from NDs in patients with head and neck cancers.
Level of Evidence
4 Laryngoscope, 130: 1947–1953, 2020
Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, ...and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome.
A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies.
Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration.
Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients’ factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery).
To investigate the various clinical and thyroid dosimetric parameters that could predict the risk of primary hypothyroidism (HT) after intensity modulated radiation therapy (IMRT) for nasopharyngeal ...carcinoma (NPC) and to determine useful thyroid dose constraints to guide radiation therapy planning.
From September 2009 to August 2012, 102 clinically euthyroid NPC patients were included in this study. All patients were treated with IMRT and randomized to induction chemotherapy followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Thyroid function was evaluated by measuring thyroid-stimulating hormone and free thyroxine at each annual follow-up visit. Various clinical and dosimetric parameters (eg, V40 percentage of thyroid volume receiving >40 Gy) were obtained. Univariate and multivariate logistic regression analyses were performed to identify predictors of HT.
Median follow-up was 48.8 months. Among the 102 patients, 44 (43.1%) developed HT within 2 years after radiation therapy. The median time to HT was 36.7 months (range, 24.9-49.0 months). The 1-year and 2-year cumulative incidence rates of HT were 33% and 44.5%, respectively. Univariate analysis revealed that younger age, early T stage, minimum dose to the thyroid gland, V40, and V45 were associated with HT. On multivariate analysis, younger age (P=.017), early T stage (P=.005), and V40 (P=.009) remained statistically significant. Patients with V40 > 85% had significantly higher cumulative incidence rates of HT than patients with V40 ≤ 85% (P=.007).
Thyroid V40 is predictive of primary HT after IMRT for NPC, and V40 ≤ 85% can be a useful dose constraint to adopt during IMRT planning without compromising tumor coverage.
The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent ...organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference.
A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement.
Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed.
Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk.
Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in ...nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC.
Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively.
Median follow-up was 5.0 years. The HR for PFS was 0.70 95% confidence interval (CI), 0.56-0.86;
= 0.0009; 9.3% absolute benefit at 5 years in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99;
= 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90;
= 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01;
= 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected.
This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control.
.
Purpose
Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure ...patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients.
Methods
Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data.
Results
Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure.
Conclusions
There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.
Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding ...normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions.
A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement.
The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints).
This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
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