Distinctive mucositis and feeding-tube dependency in cetuximab plus radiotherapy for head and neck cancer
01 Feb 2015-Japanese Journal of Clinical Oncology (Oxford University Press)-Vol. 45, Iss: 2, pp 183-188
TL;DR: Prophylactic percutaneous endoscopic gastrostomy is recommended because most patients receiving cetuximab and radiotherapy for locally advanced head and neck squamous cell carcinoma have Grade ≥ 3 mucositis with distinctive features.
Abstract: Objective Prophylactic percutaneous endoscopic gastrostomy may be considered before chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma, because severe mucositis is a common complication. We evaluated the mucosal findings and necessity of prophylactic percutaneous endoscopic gastrostomy in patients with head and neck squamous cell carcinoma receiving cetuximab and radiotherapy. Methods Fourteen consecutive patients with locally advanced head and neck squamous cell carcinoma receiving cetuximab and radiotherapy were analyzed. Results Patients' backgrounds were as follows: male/female, 8/6; median age, 64.5 years (range, 35-83 years); performance status, 0/1, 9/5. Primary tumor sites included the oropharynx, hypopharynx and larynx in four, seven and three patients, respectively. Patients completed a median of eight cetuximab cycles. All patients received three-dimensional conformal radiotherapy (median dose, 70 Gy). Thirteen patients were treated with elective neck irradiation at the ipsilateral (n = 3) or bilateral (n = 10) nodes. Grade ≥ 3 mucositis/stomatitis (clinical examination) occurred in 85.7% patients (n = 12). The median irradiation dose was 33 Gy at the Grade 3 mucositis onset. Eight patients showed mucositis with distinctive features, a wide range of white-coated lesions with a clear border; hypopharyngeal atresia was observed in two patients. Prophylactic percutaneous endoscopic gastrostomy was performed in 11 patients, and 11 patients (78.6%) actually required nutritional support because of Grade ≥ 3 mucositis/stomatitis (functional/symptomatic). Conclusions Prophylactic percutaneous endoscopic gastrostomy is recommended because most patients receiving cetuximab and radiotherapy for locally advanced head and neck squamous cell carcinoma have Grade ≥ 3 mucositis with distinctive features.
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01 Jan 2008
TL;DR: In this paper, the authors evaluated clinical factors that are associated with and might predict severe late toxicity after concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN).
Abstract: Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 p...
207 citations
TL;DR: The interesting properties of metformin such as radioprotection, radiomitigation and radiosensitization could make it an interesting adjuvant for clinical radiotherapy, as well as an interesting candidate for mitigation of radiation injury after a radiation disaster.
Abstract: BACKGROUND: Nowadays, ionizing radiation is used for several applications in medicine, industry, agriculture, and nuclear power generation. Besides the beneficial roles of ionizing radiation, there are some concerns about accidental exposure to radioactive sources. The threat posed by its use in terrorism is of global concern. Furthermore, there are several side effects to normal organs for patients who had undergone radiation treatment for cancer. Hence, the modulation of radiation response in normal tissues was one of the most important aims of radiobiology. Although, so far, several agents have been investigated for protection and mitigation of radiation injury. Agents such as amifostine may lead to severe toxicity, while others may interfere with radiation therapy outcomes as a result of tumor protection. Metformin is a natural agent that is well known as an antidiabetic drug. It has shown some antioxidant effects and enhances DNA repair capacity, thereby ameliorating cell death following exposure to radiation. Moreover, through targeting endogenous ROS production within cells, it can mitigate radiation injury. This could potentially make it an effective radiation countermeasure. In contrast to other radioprotectors, metformin has shown modulatory effects through induction of several genes such as AMPK, which suppresses reduction/ oxidation (redox) reactions, protects cells from accumulation of unrepaired DNA, and attenuates initiation of inflammation as well as fibrotic pathways. Interestingly, these properties of metformin can sensitize cancer cells to radiotherapy. CONCLUSION: In this article, we aimed to review the interesting properties of metformin such as radioprotection, radiomitigation and radiosensitization, which could make it an interesting adjuvant for clinical radiotherapy, as well as an interesting candidate for mitigation of radiation injury after a radiation disaster. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
58 citations
TL;DR: An overview of the toxicity profile of the different systemic agents is provided and a perspective into the future of SCCHN treatment is provided.
Abstract: Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used along with radiation and surgery, with cisplatin being the standard of care choice of therapy. When contraindications to cisplatin exist, other agents such as carboplatin, taxanes, 5-fluorouracil, and cetuximab are used. Similarly, in the advanced or metastatic setting, platinum agents, taxanes and cetuximab have been predominantly utilized. With the recent approval of novel agents such as pembrolizumab and nivolumab, and their distinct toxicity profiles, an understanding of the potential sequelae of the different systemic agents is essential to the careful selection of agents in the advanced disease setting. Going forward, choosing novel agents will be weighed against traditional chemotherapy, and understanding the toxicities at stake is critical in this process. In addition to providing an overview of the toxicity profile of the different systemic agents, we also provide a perspective into the future of SCCHN treatment.
29 citations
Cites background from "Distinctive mucositis and feeding-t..."
...However, thus far dding TPF to cisplatin based CCRT has not been shown to be supeior over cisplatin-based CCRT alone (Haddad et al., 2013; Cohen t al., 2014; Hitt et al., 2014; Zhang et al., 2015; Budach et al., 2016)....
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TL;DR: Regardless of p16 status, the addition of cetuximab to RT did not alter the incidence, time to onset, severity, or duration of mucositis and dysphagia and did not impact the frequency of feeding tube use.
27 citations
TL;DR: The literature and clinical experience across Asian countries were collated to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy.
Abstract: With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia–Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.
24 citations
Cites background or result from "Distinctive mucositis and feeding-t..."
...At the same time, as mentioned by several oncologists, the reported rates of skin toxicity and mucositis with cetuximab/RT in daily practice may be higher than that reported in the pivotal studies with this combination [15, 16]....
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...As observed in the Bonner trial [3], the incidence of grade 3–4 mucositis and dysphagia did not differ in the cetuximab/RT arm vs. RT alone, with 55.8 % vs. 51.9 % , and 26 % vs. 29.7 % respectively; while in the TREMPLIN study, the occurrence of grade 3–4 mucositis was 45 % with cetuximab/RT versus 47 % with CCRT. Asian clinical studies in Chinese [29] and Japanese [16, 30] populations have also shown a similar or sometimes worse outcome of cetuximab addition to RT, versus RT alone, upon the occurrence of mucositis in these patients....
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...According to Japanese experience, radiation dermatitis can be manageable by gentle washing and moistening of the woundhealing environment [20]....
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...Okano S, Yoshino T, Fujii M, Onozawa Y, Kodaira T, Fujii H, et al. Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck....
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...Asian clinical studies in Chinese [29] and Japanese [16, 30] populations have also shown a...
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References
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TL;DR: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity.
Abstract: Purpose To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. Methods and Materials One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64–74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. Results Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of − 14% (range, 0% to − 30%) and − 8% (range, +1% to − 22%) from baseline, respectively ( p p p Conclusions Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.
155 citations
TL;DR: Tumor control probability was significantly correlated with radiation dose, tumor progression (according to TNM), overall treatment time, and gap duration, and laryngeal cancers had a better prognosis than cancers of the oro- and nasopharynx.
Abstract: Purpose/Objective : Our goal was to analyze the repopulation of surviving tumor cells during a treatment gap in radiotherapy for head-and-neck cancer. Methods and Materials : Clinical material is based on the records of 1502 patients treated by radiotherapy alone in Maria Sklodowska-Curie Memorial Institute in Gliwice during the period between1980 and 1989. All patients had histologically confirmed squamous cell carcinoma of the larynx or pharynx. The mean gap duration was 9 days. Only 10% of patients were treated without gaps. The dose per fraction was in the range of 1.5 to 2.5 Gy. Patient data were fitted directly to the mixed linear-quadratic model using maximum-likelihood estimation. Tumor stage or tumor localization was introduced into the equation as a categorical variable. Tumor proliferation was estimated by dividing the treatment gaps into three groups: the first 2 weeks, second 2 weeks, and the period after 4 weeks of irradiation. Results : Tumor control probability was significantly correlated with radiation dose, tumor progression (according to TNM), overall treatment time, and gap duration. Laryngeal cancers had a better prognosis than cancers of the oro- and nasopharynx. Significant tumor repopulation was found after the first 2 weeks of radiotherapy. During the treatment gap, the proliferation rate was equal to 0.75 Gy/day. During the days with irradiation, repopulation was slower and equal to 0.2 Gy/day. Conclusion : The repopulation of tumor cells is faster during a gap than during the normal days of irradiation. Accelerated repopulation probably starts soon after 2 weeks of irradiation.
114 citations
TL;DR: These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years, although the late toxicity rates are relatively high.
Abstract: Purpose The feasibility of combining concomitant boost-accelerated radiation regimen (AFX-C) with cisplatin was previously demonstrated in this Phase II trial. This article reports the long-term toxicity, relapse patterns, and survival in patients with advanced head and neck carcinoma. Methods and Materials Between April and November 2000, 84 patients with Stage III–IV HNC were enrolled, and 76 patients were analyzable. Radiation consisted of 72 Gy over 6 weeks. Cisplatin dose was 100 mg/m 2 on Days 1 and 22. Tumor and clinical status were assessed, and acute-late toxicities were graded. Results The median follow-up for surviving patients is 4.3 years. The 2- and 4-year locoregional failure rates were 33% and 36%, respectively, and the 2- and 4-year survival rates were 70% and 54%, respectively. The worst overall late Grade 3 or 4 toxicity rate was 42%. The prevalence rates of a gastrostomy at any time during follow-up, at 12 months, and at 48 months were 83%, 41%, and 17%, respectively. Five of 36 patients (14%) alive and without disease at last follow-up were gastrostomy-tube dependent. Conclusion These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years. The late toxicity rates are relatively high. However, although prolonged dysphagia was noted in our preliminary report, its prevalence does decreased over time. A Phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin has completed accrual.
102 citations
TL;DR: A significant negative influence of treatment interruption was seen in glottic cancer, and a trend toward significance in node-negative supraglottic Cancer is seen in univariate analysis.
67 citations
TL;DR: Proposed revisions to the grading system and updated management guidelines described here represent important developments toward the more appropriate grading and effective management of radiation dermatitis in patients receiving cetuximab plus radiotherapy for LA SCCHN.
62 citations
"Distinctive mucositis and feeding-t..." refers background in this paper
...This interaction may manifest as a highly exacerbated inflammatory response in the oral and pharyngeal mucosa, as is proposed in skin reactions (21)....
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